He Jiankui

The He Jiankui affair is a scientific and bioethical controversy concerning the use of genome editing following its first use on humans by Chinese scientist He Jiankui, who edited the genomes of human embryos in 2018.[1][2] He became widely known on 26 November 2018[3] after he announced that he had created the first human genetically edited babies. He was listed in the Time's 100 most influential people of 2019.[4] The affair led to ethical and legal controversies, resulting in the indictment of He and two of his collaborators, Zhang Renli and Qin Jinzhou. He eventually received widespread international condemnation.

He Jiankui, working at the Southern University of Science and Technology (SUSTech) in Shenzhen, China, started a project to help people with HIV-related fertility problems, specifically involving HIV-positive fathers and HIV-negative mothers. The subjects were offered standard in vitro fertilisation services and in addition, use of CRISPR gene editing (CRISPR/Cas9), a technology for modifying DNA. The embryos' genomes were edited to remove the CCR5 gene in an attempt to confer genetic resistance to HIV.[5] The clinical project was conducted secretly until 25 November 2018, when MIT Technology Review broke the story of the human experiment based on information from the Chinese clinical trials registry. Compelled by the situation, he immediately announced the birth of genome-edited babies in a series of five YouTube videos the same day.[6][7] The first babies, known by their pseudonyms Lulu (Chinese: 露露) and Nana (娜娜), are twin girls born in October 2018, and the second birth or the third baby born was in 2019,[8][9] named Amy.[10] He reported that the babies were born healthy.[11]

His actions received widespread criticism,[12][13] and included concern for the girls' well-being.[5][14][15] After his presentation on the research at the Second International Summit on Human Genome Editing at the University of Hong Kong on 28 November 2018, Chinese authorities suspended his research activities the following day.[16] On 30 December 2019, Chinese authorities announced that he was found guilty of forging documents and unethical conduct; he was sentenced to three years in prison with a three-million-yuan fine (US$430,000).[17][18] Zhang Renli and Qin Jinzhou received an 18-month prison sentence, a 500,000-yuan fine and were banned from working in assisted reproductive technology for life.[19]

He Jiankui has been variously referred to as a "rogue scientist",[20] "China's Dr Frankenstein",[21] and a "mad genius".[22] The impact of human gene editing on resistance to HIV infection and other body functions in experimental infants remains controversial. The World Health Organization had issued three reports on the guidelines of human genome editing since 2019,[23] and the Chinese government has prepared regulations since May 2019.[24]

Origin

Since 2016, He Jiankui, then associate professor at the Southern University of Science and Technology (SUSTech) in Shenzhen, with Zhang Renli and Qin Jinzhou, have used human embryo in gene-editing technology for assisted reproductive medicine.[25] On 10 June 2017, a Chinese couple, an HIV-positive father and HIV-negative mother, pseudonymously called Mark and Grace,[26] attended a conference held by He at SUSTech. They were offered in vitro fertilisation (IVF) along with gene-editing of their embryos so as to develop innate resistance to HIV infection in their offspring. They agreed to volunteer through informed consent and the experiment was carried out in secrecy. Six other couples having similar fertility problems were subsequently recruited.[20] The couples were recruited through a Beijing-based AIDS advocacy group called Baihualin China League.[27] When later examined, the consent forms were noted as incomplete and inadequate.[26] The couple were reported to have agreed to this experiment because, by Chinese rules, normally HIV positive fathers were not allowed to have children using IVF.[28]

When the place of the clinical experiment was investigated, SUSTech declared that the university was not involved and that He had been on unpaid leave since February 2018, and his department attested that they were unaware of the research project.[29][30]

Experiment and birth

He Jiankui, the researcher, took sperm and eggs from the couples, performed in vitro fertilisation with the eggs and sperm, and then edited the genomes of the embryos using CRISPR/Cas9.[27] The editing targeted a gene, CCR5, that codes for a protein that HIV uses to enter cells.[31][32] He was trying to reproduce the phenotype of a specific mutation in the gene, CCR5-Δ32, that few people naturally have and that possibly confers innate resistance to HIV,[31] as seen in the case of the Berlin Patient.[33] However, rather than introducing the known CCR5-Δ32 mutation, he introduced a frameshift mutation intended to make the CCR5 protein entirely nonfunctional.[34] According to He, Lulu and Nana carried both functional and mutant copies of CCR5 given mosaicism inherent in the present state of the art in germ-line editing.[35] There are forms of HIV that use a different receptor instead of CCR5; therefore, the work of He did not theoretically protect Lulu and Nana from those forms of HIV.[31] He used a preimplantation genetic diagnosis process on the embryos that were edited, where three to five single cells were removed, and fully sequenced them to identify chimerism and off-target errors. He says that during the pregnancy, cell-free fetal DNA was fully sequenced to check for off-target errors, and an amniocentesis was offered to check for problems with the pregnancy, but the mother declined.[31] Lulu and Nana were born in secrecy in October 2018.[7] They were reported by He to be normal and healthy.[11]

Revelation

He Jiankui was planning to reveal his experiments and the birth of Lulu and Nana at the Second International Summit on Human Genome Editing, which was to be organized at the University of Hong Kong during 27–29 November 2018.[36] However, on 25 November 2018, Antonio Regalado, senior editor for biomedicine of MIT Technology Review, posted on the journal's website about the experiment based on He Jiankui's applications for conducting clinical trial that had been posted earlier on the Chinese clinical trials registry. At the time, He refused to comment on the conditions of the pregnancy.[6][37] Prompted by the publicity, He immediately posted about his experiment and the successful birth of the twins on YouTube in five videos the same day.[38][39] The next day, the Associated Press made the first formal news, which was most likely a pre-written account before the publicity.[1] His experiment had received no independent confirmation, and had not been peer reviewed or published in a scientific journal.[40][41][42] Soon after He's revelation, the university at which He was previously employed, the Southern University of Science and Technology, stated that He's research was conducted outside of their campus.[43] China's National Health Commission also ordered provincial health officials to investigate his case soon after the experiment was revealed.[40]

Amidst the furore, He was allowed to present his research at the Hong Kong meeting on 28 November under the title "CCR5 gene editing in mouse, monkey, and human embryos using CRISPR–Cas9". During the discussion session, He asserted, "Do you see your friends or relatives who may have a disease? They need help," and continued, "For millions of families with inherited disease or infectious disease, if we have this technology we can help them."[44] In his speech, He also mentioned about a second pregnancy under the same experiment.[11] No reports disclosed, the baby might have been born around August 2019,[45] and the birth was affirmed on 30 December when the Chinese court returned a verdict mentioning that there were "three genetically-edited babies".[46] The baby was later revealed in 2022 as Amy.[10]

Reactions and aftermath

On the news of Lulu and Nana being born, the People's Daily announced the experimental result as "a historical breakthrough in the application of gene editing technology for disease prevention."[47] But scientists at the Second International Summit on Human Genome Editing immediately developed serious concerns. Robin Lovell-Badge, head of the Laboratory of Stem Cell Biology and Developmental Genetics at the Francis Crick Institute, who moderated the session on 28 November recalled that He Jiankui did not mention human embryos in the draft summary of the presentation.[48] He received an urgent message on 25 November through Jennifer Doudna of the University of California, Berkeley, a pioneer of the CRISPR/Cas9 technology, to whom he had confided the news earlier that morning.[20] As the news already broke out before the day of the presentation, he had to be brought in by the University of Hong Kong security from his hotel. Nobel laureate David Baltimore, the chair of the organizing committee of the summit, was the first to react after He's speech, and declared his horror and dismay at his work.[48]

He did not disclose the parents' names (other than their pseudonyms Mark and Grace) and they did not make themselves available to be interviewed, so their reaction to this experiment and the ensuing controversy is not known.[27] There was widespread criticism in the media and scientific community over the conduct of the clinical project and its secrecy,[49][50] and concerns raised for the long term well-being of Lulu and Nana.[11][42] Bioethicist Henry T. Greely of Stanford Law School declared, "I unequivocally condemn the experiment,"[51] and later, "He Jiankui’s experiment was, amazingly, even worse than I first thought."[52] Kiran Musunuru, one of the experts called on to review He's manuscript and who later wrote a book on the scandal, called it a "historic ethical fiasco, a deeply flawed experiment".[53]

On the night of 26 November 122 Chinese scientists issued a statement criticizing his research. They declared that the experiment was unethical, "crazy" and "a huge blow to the global reputation and development of Chinese science".[47] The Chinese Academy of Medical Sciences made a condemnation statement on 5 January 2019 saying that:

We are opposed to any clinical operation of human embryo genome editing for reproductive purposes in violation of laws, regulations, and ethical norms in the absence of full scientific evaluation. In the rapidly developing area of genome editing technology, our scientific community should uphold the highest standards of bioethics in undertaking responsible biomedical research and applications and uphold our scientific reputation, the basic dignity of human life, and the collective integrity of our scientific community. The Chinese Government prohibits the genetic manipulation of human gametes, zygotes, and embryos for reproductive purposes ... Jiankui He's operations violated these regulations.[54]

A series of investigations was opened by He's university, local authorities, and the Chinese government. On 26 November 2018, SUSTech released a public notification on its website condemning He's conduct, mentioning the key points as:

  • The research work was conducted off-campus by Associate Professor He Jiankui without reporting to the university and the Department of Biology, and the university and the Department of Biology were unaware of it.
  • The Academic Committee of the Department of Biology considers that Associate Professor He Jiankui's use of gene editing technology for human embryo research is a serious violation of academic ethics and academic standards.
  • SUSTech strictly requires scientific research to comply with national laws and regulations and to respect and abide by international academic ethics and academic norms. The university will immediately hire authoritative experts to set up an independent committee to conduct an in-depth investigation, and will publish relevant information after the investigation.[55]

On 28 November 2018, the organising committee of the Second International Summit on Human Genome Editing, led by Baltimore, issued a statement, declaring:

At this summit we heard an unexpected and deeply disturbing claim that human embryos had been edited and implanted, resulting in a pregnancy and the birth of twins. We recommend an independent assessment to verify this claim and to ascertain whether the claimed DNA modifications have occurred. Even if the modifications are verified, the procedure was irresponsible and failed to conform with international norms. Its flaws include an inadequate medical indication, a poorly designed study protocol, a failure to meet ethical standards for protecting the welfare of research subjects, and a lack of transparency in the development, review, and conduct of the clinical procedures.[56]

On 29 January 2019, it was learned that a U.S. Nobel laureate Craig Mello interviewed He about his experiment with gene-edited babies.[57] In February 2019, He's claims were reported to have been confirmed by Chinese investigators, according to NPR News.[58] Around that time, news reported that the Chinese government may have helped fund the CRISPR babies experiment, at least in part, based on newly uncovered documents.[59][60][61]

Consequences

On 29 November 2018, Chinese authorities suspended all of He's research activities, saying his work was "extremely abominable in nature" and a violation of Chinese law.[62] He was sequestered in a university apartment under some sort of surveillance.[63][64][65] On 21 January 2019, He was fired from his job at SUSTech and his teaching and research work at the university was terminated.[66] The same day, the Guangdong Province administration investigated the "gene editing baby incident", which is explicitly prohibited by the state.[67] On 30 December 2019, the Shenzhen Nanshan District People's Court sentenced He Jiankui to three years in prison and with a fine of 3 million RMB (about US$434,000 in 2019).[17][18]

Among the collaborators, only two were indicted – Zhang Renli of the Guangdong Academy of Medical Sciences and Guangdong General Hospital, received a two-year prison sentence and a 1-million RMB (about US$145,000) fine, and Qin Jinzhou of the Southern University of Science and Technology received an 18-month prison sentence and a 500,000 RMB (about US$72,000) fine.[68] The three were found guilty of having "forged ethical review documents and misled doctors into unknowingly implanting gene-edited embryos into two women."[69] Zhang and Qin were officially banned from working in assisted reproductive technology for life.[19] In April 2022, He was released from prison.[28][70]

On 26 November 2018, The CRISPR Journal published ahead of print an article by He, Ryan Ferrell, Chen Yuanlin, Qin Jinzhou, and Chen Yangran in which the authors justified the ethical use of CRISPR gene editing in humans.[71] As the news of CRISPR babies broke out, the editors reexamined the paper and retracted it on 28 December, announcing:

[It] has since been widely reported that Dr. He conducted clinical studies involving germline editing of human embryos, resulting in several pregnancies and two alleged live births. This was most likely in violation of accepted bioethical international norms and local regulations. This work was directly relevant to the opinions laid out in the Perspective; the authors' failure to disclose this clinical work manifestly impacted editorial consideration of the manuscript.[72]

Michael W. Deem, an American bioengineering professor at Rice University and his doctoral advisor was involved in the research, and was present when people involved in the study gave consent.[27] He was the only non-Chinese out of 10 authors listed in the manuscript submitted to Nature.[34] Deem came under investigation by Rice University after news of the work was made public.[73][74] As of 2022, the university never issued any information on his conduct. He resigned from the university in 2020,[28] and pursued a business by creating a bioengineering and energy consultant company called Certus LLC.[75]

Stanford University also investigated its faculty of He's confidants including William Hurlbut, Matthew Porteus, and Stephen Quake, his main mentor in gene editing. The university's review committee concluded that the accused "were not participants in [He Jiankui’s] research regarding genome editing of human embryos for intended implantation and birth and that they had no research, financial or organizational ties to this research."[76]

In response to He's work, the World Health Organization, formed a committee comprising "a global, multi-disciplinary expert panel" called the Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing "to examine the scientific, ethical, social and legal challenges associated with human genome editing (both somatic and germline)" in December 2018.[77][78] In 2019, it issued a call to halt all work on human genome editing, and launched a global registry to track research in the field.[79][80][81] It had issued three reports for the recommended guidelines on human genome editing since 2019.[23] As of 2021, the committee stood by the grounds that while somatic gene therapies have become useful in several disease, germline and heritable human genome editing is still with risks,[82] and should be banned.[83]

In May 2019, Chinese government prepared gene-editing regulations stressing that anyone found manipulating the human genome by genome-editing techniques would be held responsible for any related adverse consequences.[24] The Civil Code of the People's Republic of China was amended in 2020 that added Article 1009 which states: "any medical research activity associated with human gene and human embryo must comply with the relevant laws, administrative regulations and national regulation, must not harm individuals and violate ethical morality and public interest."[84] It was enacted on 1 January 2021.[85] A draft of the 11th Amendment to the Chinese Criminal Code in 2020 has incorporated three types of crime: the illegal practice of human gene editing, human embryo cloning and severe endangering of the security of human genetic resources; with penalties of imprisonment of up to 7 years and a fine.[84]

As of December 2021, Vivien Marx reported in the Nature Biotechnology article that both children are healthy.[23]

Ethical controversies

Ethics of genome manipulation

Genome manipulations can be done at two levels: somatic (grown-up cells of the general body) and germline (sex cells and embryos for reproduction). The development of CRISPR gene editing enabled both somatic and germline editing (such as in assisted reproductive technology).[86] There is no prohibition on somatic gene editing since the practice is generally covered by the available regulations.[87] Prior to He's affair, there was already concern that it was possible to make genetically modified babies and such experiments would have ethical issues as the safety and success were not yet warranted by any study,[88][89] and genetic enhancement of individual would be possible.[90] Pioneer gene-editing scientists had warned in 2015 that "genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable. Such research could be exploited for non-therapeutic modifications."[91] As Janet Rossant of the University of Toronto noted in 2018: "It has also raised ethical concerns, particularly with regard to the possibility of generating heritable changes in the human genome – so-called germline gene editing."[92] In 2017, the National Academies of Sciences, Engineering, and Medicine published a report "Human Genome Editing: Science, Ethics and Governance" that endorsed germline gene editing in "the absence of reasonable alternatives" of disease management and to "improve IVF procedures and embryo implantation rates and reduce rates of miscarriage."[93] However, the Declaration of Helsinki had stated that early embryo genome-editing for fertility purposes is unethical.[94]

The American Society of Human Genetics had declared in 2017 that the basic research on in vitro human genome editing on embryos and gametes should be promoted but that "At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy."[86] In July 2018, the Nuffield Council on Bioethics published a policy document titled Genome Editing and Human Reproduction: Social and Ethical Issues in which it advocated human germline editing saying that it "is not 'morally unacceptable in itself' and could be ethically permissible in certain circumstances" when there are sufficient safety measures.[95] The moral justification created critical debates.[96][97][98] The United States National Institutes of Health Somatic Cell Genome Editing Consortium held that it "strictly focused on somatic editing; germline editing is not only excluded as a goal but is also considered to be an unacceptable outcome that should be carefully prevented."[99]

The Chinese law Measures on Administration of Assisted Human Reproduction Technology (2001) prohibits any genetic manipulation of human embryos for reproductive purposes and allow assisted reproductive technology to be performed only by authorized personnel.[100] On 7 March 2017, He Jiankui applied for ethics approval from Shenzhen HarMoniCare Women and Children's Hospital. In the application, He claimed that the genetically edited babies would be immune to HIV infection, in addition to smallpox and cholera, commenting: "This is going to be a great science and medicine achievement ever since the IVF technology which was awarded the Nobel Prize in 2010, and will also bring hope to numerous genetic disease patients." It was approved and signed by Lin Zhitong, the hospital administrator and one-time Director of Direct Genomics, a company established by He.[20] Upon an inquiry, the hospital denied such approval. The hospital's spokesperson declared that there were no records of such ethical approval, saying, "[The] gene editing process did not take place at our hospital. The babies were not born here either."[101] It was later confirmed that the approval certificate was forged.[102][103]

Sheldon Krimsky of Tufts University reported that "[He Jiankui] is not a medical doctor, but rather received his doctorate in biophysics and did postdoctoral studies in gene sequencing; he lacks training in bioethics."[104] However, He was aware of the ethical issues. On 5 November 2018, He and his collaborators submitted a manuscript on ethical guidelines for reproductive genome editing titled "Draft Ethical Principles for Therapeutic Assisted Reproductive Technologies" to The CRISPR Journal.[105] It was published on 26 November, soon after news of the human experiment broke out. The journal made an inquiry concerning conflicts of interests, which was not disclosed by He. With no justification from He, the journal retracted the paper with a comment that it "was most likely in violation of accepted bioethical international norms and local regulations."[106]

Although there were no specific laws in China on gene editing in humans, He Jiankui violated the available guideline on handling human embryos.[107] According to the Guidelines for Ethical Principles in Human Embryonic Stem Cell Research (2003) of the Ministry of Science and Technology and the National Health Commission of China:

Research in human embryonic stem cells shall be in compliance with the following behavioral norms:

  1. Where blastula is obtained from external fertilization, somatic nucleus transplantation, unisexual duplicating technique or genetic modification, the culture period in vitro shall not exceed 14 days from the day of fecundation or nuclear transplantation.[100]

He Jiankui also attended an important meeting on "The ethics and societal aspects of gene editing" in January 2017 organized by Jennifer Doudna and William Hurlbut of Stanford University.[108] Upon invitation from Doudna, He presented a topic on "Safety of Human Gene Embryo Editing" and later recalled that "There were very many thorny questions, triggering heated debates, and the smell of gunpowder was in the air."[20]

The consent form of the experiment titled "Informed Consent" also indicates dubious statements. The aim of the study was presented as "an AIDS vaccine development project", even though the study was not about vaccines. Present was technical jargon which would be incomprehensible to a layperson.[47][26] One of the more peculiar statement is that if the participants decide to abort the experiment "in the first cycle of IVF until 28 days post-birth of the baby", they would have to "pay back all the costs that the project team has paid for you. If the payment is not received within 10 calendar days from the issuance of the notification of violation by the project team, another 100,000 RMB (about US$14,000) of fine will be charged."[109] This violates the voluntary nature of the participation.[47]

Medical ethics

CRISPR gene editing technology in humans has the potential to cause profound social impacts,[110] such as in the long-term prevention of diseases in humans.[111] However, He's human experiments raised ethical concerns the effect are unknown on future generations.[110] Ethical concerns have been raised relative to the four ethical criteria of autonomy, justice, beneficence, and non-maleficence,[112][111] first postulated by Tom Beauchamp and James Childress in Principles of Biomedical Ethics.[113]

The ethical principle of autonomy requires that individuals have the ability and comprehensive information to make their own decisions based on their values and beliefs. [112] He violated this by failing to inform patients of potential risks, including off-target mutations that might be a threat to the twins' lives.[114]

Since He had forged the approval certificate from the hospital's Director of Direct Genomics, the procedure was likely "unlawful",[114] which is against the principle of non-maleficence.[112] Off-target mutations are likely to start at undesired sites, causing cell death or cell transformation.[115] Sonia Ouagrham-Gormley, an associate professor in the Schar School of Policy and Government at George Mason University, and Kathleen Vogel, a professor in the School for the Future of Innovation in Society at Arizona State University, stated that the procedure was "unnecessary" and "risks the safety of the patients". The researchers criticized He's unethical action by presenting the fact that the prevention of HIV transmission from parents to newborn babies can be safely achieved with existing standard methods, such as sperm washing and caesarian section delivery.[114]

The principle of justice argues that individuals should have the right to receive the same amount of care from medical providers regardless of their social and economic background.[112] Beneficence requires healthcare providers to maximize benefits and put the benefit of the patients first.[112] He's intervention in the twins' genes cannot be justified, and the risk-benefit is unacceptable.[116] He paid the couple $40,000 to ensure that they would keep his operation confidential. This action can be viewed as an inducement and violates China's regulations on the prohibition of genetic manipulation of human gametes, zygotes, and embryos for reproductive purposes; HIV carriers being not allowed to have assisted reproductive technologies, and the manipulation of a human embryo for research being only permitted within 14 days.[116]

Thus, while genome editing in humans has potential as an effective and cost-efficient method for manipulating genes within living cells, it requires more research and transparent procedures to be ethically justified.[111]

Scientific issues

Effects of mutations

It is an established fact that C-C chemokine receptor type 5 (CCR5) is a protein essential for HIV infection of the white blood cells by acting as co-receptor to HIV. Mutation in the gene CCR5 (called CCR5Δ32 because the mutation is specifically a deletion of 32 base pairs in human chromosome 3) renders resistance to HIV.[117][118] Resistance is higher when mutations are in two copies (homozygous alleles) and in only one copy (heterozygous alleles) the protection is very weak and slow. Not all homozygote individuals are completely resistant.[119] In natural population, CCR5Δ32 homozygotes are rarer than heterozygotes.[120] In 2007, Timothy Ray Brown (dubbed the Berlin patient) became the first person to be completely cured of HIV infection following a stem cell transplant from a CCR5Δ32 homozygous donor.[121]

He Jiankui overlooked these facts. Two days after Lulu and Nana were born, their DNA were collected from blood samples of their umbilical cord and placenta. Whole genome sequencing confirmed the mutations.[122] However, available sources indicate that Lulu and Nana are carrying incomplete CCR5 mutations. Lulu carries a mutant CCR5 that has a 15-bp in-frame deletion only in one chromosome 3 (heterozygous allele) while the other chromosome 3 is normal; and Nana carries a homozygous mutant gene with a 4-bp deletion and a single base insertion.[123] He therefore failed to achieve the complete 32-bp deletion.[107] Moreover, Lulu has only heterozygous modification which is not known to prevent HIV infection.[118] Because the babies' mutations are different from the typical CCR5Δ32 mutation it is not clear whether or not they are prone to infection.[123] There are also concerns about adverse effect called off-target mutation in CRISPR/Cas9 editing and mosaicism, a condition in which many different cells develop in the same embryo.[122] Off-target mutation may cause health hazards, while mosaicism may create HIV susceptible cells. Fyodor Urnov, Director at the Altius Institute for Biomedical Sciences at Washington, asserted that "This [off-target mutation] is a key problem for the entirety of the embryo-editing field, one that the authors sweep under the rug here," and continued, "They [He's team] should have worked and worked and worked until they reduced mosaicism to as close to zero as possible. This failed completely. They forged ahead anyway."[34]

He's data on Lulu and Nana's mutation alignment (in Sanger chromatogram) showed three modifications, while two should be expected. Particularly in Lulu, the mutation is much more complex than He's report. There were three different combinations of alleles: two normal copies of CCR5, one normal copy and one with a 15-bp deletion, and one normal copy and an unknown large insertion.[107] But George Church of Harvard University, in an interview with Science, explained that off-target mutations may not be dangerous, and that there is no need to reduce mosaicism excessively, saying, "There's no evidence of off-target causing problems in animals or cells. We have pigs that have dozens of CRISPR mutations and a mouse strain that has 40 CRISPR sites going off constantly and there are off-target effects in these animals, but we have no evidence of negative consequences." As to mosaicism, he said, "It may never be zero. We don’t wait for radiation to be zero before we do positron emission tomography scans or x-rays."[124]

In February 2019, scientists reported that Lulu and Nana may have inadvertently (or perhaps, intentionally[61]) had their brains altered,[125] since CCR5 is linked to improved memory function in mice,[126] as well as enhanced recovery from strokes in humans.[127] Although He Jiankui stated during the Second International Summit on Human Genome Editing, that he was against using genome editing for enhancement,[128] he also acknowledged that he was aware of the studies linking CCR5 to enhanced memory function.[35]

In June 2019, researchers incorrectly suggested that the purportedly genetically edited humans may have been mutated in a way that shortens life expectancy.[129][130] Rasmus Nielsen and Wei Xinzhu, both at the University of California, Berkeley, reported in Nature Medicine of their analysis of the longevity of 409,693 individuals from British death registry (UK BioBank) with the conclusion that two copies of CCR5Δ32 mutations (homozygotes) were about 20% more likely than the rest of the population to die before they were 76 years of age.[131] The research finding was widely publicized in the popular and scientific media.[132][133] However, the article overlooked sampling bias in UK Biobank's data, resulting in an erroneous interpretation, and was retracted four months later.[134][135]

Rejections from peer-reviewed journals

Scientific works are normally published in peer-reviewed journals, but He failed to do so regarding the birth of gene-edited babies. This was one of the grounds on which He was criticized.[30][136] It was later reported that He did submit two manuscripts to Nature and the Journal of the American Medical Association, which were both rejected, mainly on ethical issues.[137] He's first manuscript titled "Birth of Twins After Genome Editing for HIV Resistance" was submitted to Nature on 19 November. He shared copies of the manuscript to the Associated Press, which he further allowed to document his works.[138] In an interview, Hurlbut opined that the condemnation of He's work would have been less harsh if the study had been published, and said, "If it had been published, the publishing process itself would have brought a level of credibility because of the normal scrutiny involved; the data analysis would have been vetted."[139]

The scientific manuscripts of He were revealed when an anonymous source sent them to the MIT Technology Review, which reported them on 3 December 2019.[34][140]

The first successful gene-editing experiment of CCR5 in humans was in 2014. A team of researchers at the University of Pennsylvania, Philadelphia, Albert Einstein College of Medicine, New York, and Sangamo BioSciences, California, reported that they modified CCR5 on the blood cells (CD4 T cells) using zinc-finger nuclease which they introduced (infused) into 12 individuals with HIV.[141] After complete treatment, the patients showed decreased viral load, and in one, HIV disappeared.[142] The result was published in The New England Journal of Medicine.[143]

Chinese scientists have successfully used CRISPR editing to create mutant mice and rats since 2013.[144][145] The next year they reported successful experiment in monkeys involving a removal of two key genes (PPAR-γ and RAG1) that play roles in cell growth and cancer development.[146] One of the leading researchers, Yuyu Niu later collaborated with He Jiankui in 2017 to test the CRISPR editing of CCR5 in monkeys, but the outcome was not fully assessed or published. Niu later commented that they "had no idea he was going to do this in a human being."[147] In 2018, his team reported an induction of mutation to produce muscular dystrophy,[148] and simultaneously by another independent Chinese team an induction of growth retardation in monkeys using CRISPR editing.[149] In February 2018, scientists at the Chinese Academy of Sciences reported the creation of five identical cloned gene-edited monkeys, using the same cloning technique that was used by them to create the first cloned primates Zhong Zhong and Hua Hua in 2018[150] and Dolly the sheep.[151] The mutant monkeys and clones were made for understanding several medical diseases and not for disease resistance.[152][153]

The first clinical trials of CRISPR-Cas9 for the treatment of genetic blood disorders was started in August 2018. The study was jointly conducted by CRISPR Therapeutics, a Swiss-based company, and Vertex Pharmaceuticals, headquartered in Boston.[154] The result was first announced on 19 November 2019 which states that the first two patients, one with β-thalassemia and the other with sickle cell disease, were treated successfully.[155] Under the same project, a parallel study on 6 individuals with sickle cell disease was also conducted at Harvard Medical School, Boston. In both studies, the gene involved in blood cell formation BCL11A was modified in the bone marrow extracted from the individuals.[156] Both the studies were simultaneously published in The New England Journal of Medicine on 21 January 2021 in two papers.[157][158] The individuals have not complained the symptoms and needed blood transfusion normally required in such disease, but the method is arduous and poses high risk of infection in the bone marrow, to which David Rees at King's College Hospital commented, "Scientifically, these studies are quite exciting. But it’s hard to see this being a mainstream treatment in the long term."[156]

In June 2019, Denis Rebrikov at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology in Moscow announced through Nature that he was planning to repeat He's experiment once he got official approval from the Russian Ministry of Health and other authorities. Rebrikov asserted that he would use safer and better method than that of He, saying, "I think I'm crazy enough to do it."[159] In a subsequent report on 17 October, Rebrikov said that he was approached by a deaf couple for help. He already started in vitro experiment to repair a gene that causes deafness, GJB2, using CRISPR.[160]

In 2019, the Abramson Cancer Center of the University of Pennsylvania in US announced the use of the CRISPR technology to edit cancer genes in humans,[161] and the results of the phase I clinical trial in 2020.[162] The study started in 2018 with an official registration in the US clinical trials registry.[163] The report in the journal Science indicates three individuals in their 60s with advanced refractory cancer, two of them with the blood cancer (multiple myeloma) and one with tissue cancer (sarcoma), were treated with their own cancer cells after CRISPR editing.[164] The experiment was based on CAR T-cell therapy by which the T cells, obtained from the individuals were removed of three genes involved in cancer and were added a gene CTAG1B that produces an antigen NY-ESO-1. When the edited cells were introduced back into the individuals, the antigens attack the cancer cells.[165] Although the results were acclaimed as the first "success of gene editing and cell function"[162] in cancer research and "an important milestone in the development and clinical application of gene-edited effector cell therapy,"[166] it was far from curing the diseases. One died after the clinical trial, and the other two had recurrent cancer.[167]

A similar clinical trial was reported by a team of Chinese scientists at the Sichuan University and their collaborators in 2020 in Nature Medicine.[168] Here they removed only one gene (PDCD1 that produces the protein PD-1) in the T cells from 12 individuals having late-stage lung cancer. The study was found to be safe and effective.[169] However, the edited T cells were not fully efficient and disappeared in most individuals, indicating that the treatments were not completely successful.[170]

See also

References

  1. 1 2 Greely, Henry T (2019). "CRISPR'd babies: human germline genome editing in the 'He Jiankui affair'". Journal of Law and the Biosciences. 6 (1): 111–183. doi:10.1093/jlb/lsz010. PMC 6813942. PMID 31666967.
  2. ↑ Cyranoski, David (22 January 2019). "CRISPR-Baby Scientist Fired by University". Nature. doi:10.1038/d41586-019-00246-2. S2CID 159097706. Retrieved 9 January 2020.
  3. ↑ Cyranoski, David; Ledford, Heidi (26 November 2018). "Genome-edited baby claim provokes international outcry". Nature. 563 (7733): 607–608. Bibcode:2018Natur.563..607C. doi:10.1038/d41586-018-07545-0. PMID 30482929. S2CID 53768039.
  4. ↑ "Scientist He Jiankui Among TIME'S 100 Most Influential". CodeBlue. 19 April 2019. Retrieved 27 March 2022.
  5. 1 2 "China Orders Investigation After Scientist Claims First Gene-Edited Babies". The New York Times. Reuters. 26 November 2018. Archived from the original on 27 November 2018. Retrieved 26 November 2018.
  6. 1 2 Regalado, Antonio (25 November 2018). "Chinese scientists are creating CRISPR babies". MIT Technology Review.
  7. 1 2 Bulluck, Pam (14 April 2019). "Gene-Edited Babies: What a Chinese Scientist Told an American Mentor". The New York Times. Retrieved 14 April 2019.
  8. ↑ Begley, Sharon; Joseph, Andrew (17 December 2018). "The CRISPR Shocker: How Genome-Editing Scientist He Jiankui Rose from Obscurity to Stun the World". Stat News. Retrieved 17 December 2018.
  9. ↑ Begley, Sharon (26 November 2018). "Claim of CRISPR'd baby girls stuns genome editing summit". Stat News. Archived from the original on 27 November 2018. Retrieved 26 November 2018.
  10. 1 2 Gutierrez C., Nicolas (29 June 2022). "What's next for the gene-edited children from CRISPR trial in China?". New Scientist. Retrieved 9 January 2023.
  11. 1 2 3 4 Begley, Sharon (28 November 2018). "Amid Uproar, Chinese Scientist Defends Creating Gene-Edited Babies". STAT.
  12. ↑ Kolata, Gina; Belluck, Pam (5 December 2018). "Why Are Scientists So Upset About the First Crispr Babies? - Only because a rogue researcher defied myriad scientific and ethical norms and guidelines. We break it down". The New York Times. Retrieved 5 December 2018.
  13. ↑ The Editorial Board (28 January 2019). "Should Scientists Toy With the Secret to Life? - The gene-editing technology Crispr has the power to remake life as we know it. Questions about how to use it concern everyone". The New York Times. Retrieved 29 January 2019.
  14. ↑ Regalado, Antonio (25 November 2018). "Exclusive: Chinese scientists are creating CRISPR babies - A daring effort is under way to create the first children whose DNA has been tailored using gene editing". MIT Technology Review. Archived from the original on 27 November 2018. Retrieved 26 November 2018.
  15. ↑ Cyranoski, David (27 November 2018). "How the genome-edited babies revelation will affect research - Some scientists worry the startling claim will lead to knee-jerk regulations and damage the public's trust in gene editing". Nature. doi:10.1038/d41586-018-07559-8. S2CID 158314199. Archived from the original on 27 November 2018. Retrieved 27 November 2018.
  16. ↑ Jiang, Steven; Regan, Helen; Berlinger, Joshua (29 November 2018). "China suspends scientists who claim to have produced first gene-edited babies". CNN News. Retrieved 29 November 2018.
  17. 1 2 Wee, Sui-Lee (30 December 2019). "Chinese Scientist Who Genetically Edited Babies Gets 3 Years in Prison - He Jiankui's work was also carried out on a third infant, according to China's state media, in a new disclosure that is likely to add to the global uproar over such experiments". The New York Times. Retrieved 30 December 2019.
  18. 1 2 Yee, Isaac; Hollingsworth, Julia (30 December 2019). "Chinese gene-editing scientist jailed for 3 years". CNN News. Retrieved 30 December 2019.
  19. 1 2 "China convicts 3 researchers involved in gene-edited babies". AP NEWS. 20 April 2021. Retrieved 27 March 2022.
  20. 1 2 3 4 5 Cohen, Jon (2 August 2019). "Inside the circle of trust". Science. 365 (6452): 430–437. Bibcode:2019Sci...365..430C. doi:10.1126/science.365.6452.430. PMID 31371593.
  21. ↑ Yan, Sophia (28 November 2018). "China's 'Dr Frankenstein' says second woman in early pregnancy with gene-edited babies". The Telegraph. Retrieved 10 January 2020.
  22. ↑ Low, Zoe (27 November 2018). "China's gene editing Frankenstein had dreams of being Chinese Einstein". South China Morning Post. Retrieved 10 January 2020.
  23. 1 2 3 Marx, Vivien (24 November 2021). "The CRISPR children". Nature Biotechnology. 39 (12): 1486–1490. doi:10.1038/s41587-021-01138-5. PMID 34819659. S2CID 244653054.
  24. 1 2 Cyranoski, David (20 May 2019). "China set to introduce gene-editing regulation following CRISPR-baby furore - The draft rules mean that anyone who manipulates human genes in adults or embryos is responsible for adverse outcomes". Nature. doi:10.1038/d41586-019-01580-1. PMID 32424191. S2CID 182604140. Retrieved 20 May 2019.
  25. ↑ "The untold story of the 'circle of trust' behind the world's first gene-edited babies". Science.org. Retrieved 18 April 2022.
  26. 1 2 3 Caplan, Arthur (2019). "Getting serious about the challenge of regulating germline gene therapy". PLOS Biology. 17 (4): e3000223. doi:10.1371/journal.pbio.3000223. PMC 6490874. PMID 31039143.
  27. 1 2 3 4 Marchione, Marilyn (26 November 2018). "Chinese researcher claims first gene-edited babies". AP NEWS.
  28. 1 2 3 Regalado, Antonio (4 April 2022). "The creator of the CRISPR babies has been released from a Chinese prison". MIT Technology Review. Retrieved 5 April 2022.
  29. ↑ 南科大：贺建奎2月已停薪留职 项目违背学术伦理. Sina. 26 November 2018. Retrieved 28 November 2018.
  30. 1 2 Cyranoski, David; Ledford, Heidi (26 November 2018). "Genome-edited baby claim provokes international outcry". Nature. 563 (7733): 607–608. Bibcode:2018Natur.563..607C. doi:10.1038/d41586-018-07545-0. PMID 30482929. S2CID 53768039.
  31. 1 2 3 4 Belluck, Pam (28 November 2018). "Chinese Scientist Who Says He Edited Babies' Genes Defends His Work". The New York Times. Retrieved 29 November 2018.
  32. ↑ de Silva E, Stumpf MP (December 2004). "HIV and the CCR5-Delta32 resistance allele". FEMS Microbiology Letters. 241 (1): 1–12. doi:10.1016/j.femsle.2004.09.040. PMID 15556703.
  33. ↑ ""Menschenversuche": Geburt genmanipulierter Babys verkündet". Stern (in German). 26 November 2018.
  34. 1 2 3 4 Regalado, Antonio (3 December 2019). "China's CRISPR babies: Read exclusive excerpts from the unseen original research - He Jiankui's manuscript shows how he ignored ethical and scientific norms in creating the gene-edited twins Lulu and Nana". MIT Technology Review. Retrieved 3 December 2019.
  35. 1 2 Cohen, Jon (2019). "Did CRISPR help—or harm—the first-ever gene-edited babies?". Science. doi:10.1126/science.aay9569.
  36. ↑ Galvin, Molly (26 November 2018). "Statement from the Organizing Committee on Reported Human Embryo Genome Editing". NationalAcademies.org. Retrieved 8 January 2020.
  37. ↑ Regalado, Antonio (25 November 2018). "Exclusive: Chinese scientists are creating CRISPR babies - A daring effort is under way to create the first children whose DNA has been tailored using gene editing". MIT Technology Review. Archived from the original on 27 November 2018. Retrieved 26 November 2018.
  38. ↑ The He Lab (25 November 2018), About Lulu and Nana: Twin Girls Born Healthy After Gene Surgery As Single-Cell Embryos, retrieved 26 April 2019
  39. ↑ Dyer, Owen (2018). "Researcher who edited babies' genome retreats from view as criticism mounts". BMJ. 363: k5113. doi:10.1136/bmj.k5113. PMID 30504437. S2CID 54485094.
  40. 1 2 "China Orders Investigation After Scientist Claims First Gene-Edited Babies". The New York Times. Reuters. 26 November 2018. Archived from the original on 27 November 2018. Retrieved 26 November 2018.
  41. ↑ Begley, Sharon (26 November 2018). "Claim of CRISPR'd baby girls stuns genome editing summit". Stat News. Archived from the original on 27 November 2018. Retrieved 26 November 2018.
  42. 1 2 Cyranoski, David (27 November 2018). "How the genome-edited babies revelation will affect research - Some scientists worry the startling claim will lead to knee-jerk regulations and damage the public's trust in gene editing". Nature. doi:10.1038/d41586-018-07559-8. S2CID 158314199. Archived from the original on 27 November 2018. Retrieved 27 November 2018.
  43. ↑ Staff (26 November 2018). "Southern University of Science and Technology Statement On the Genetic Editing of Human Embryos Conducted by Dr. Jiankui HE - In the Focus - SUSTC". Southern University of Science and Technology (in Chinese). Archived from the original on 26 November 2018. Retrieved 27 November 2018.
  44. ↑ Cyranoski, David (2018). "CRISPR-baby scientist fails to satisfy critics". Nature. 564 (7734): 13–14. Bibcode:2018Natur.564...13C. doi:10.1038/d41586-018-07573-w. PMID 30514937.
  45. ↑ Cyranoski, David (2019). "The CRISPR-baby scandal: what's next for human gene-editing". Nature. 566 (7745): 440–442. Bibcode:2019Natur.566..440C. doi:10.1038/d41586-019-00673-1. PMID 30809070.
  46. ↑ Huaxia (30 December 2019). "Three jailed in China's "gene-edited babies" trial - Xinhua | English.news.cn". Xinhuanet.com. Archived from the original on 30 December 2019. Retrieved 9 January 2020.
  47. 1 2 3 4 Li, Jing-ru; Walker, Simon; Nie, Jing-bao; Zhang, Xin-qing (2019). "Experiments that led to the first gene-edited babies: the ethical failings and the urgent need for better governance". Journal of Zhejiang University Science B. 20 (1): 32–38. doi:10.1631/jzus.B1800624. PMC 6331330. PMID 30614228.
  48. 1 2 Lovell-Badge, Robin (2019). "CRISPR babies: a view from the centre of the storm". Development. 146 (3): dev175778. doi:10.1242/dev.175778. PMID 30728161.
  49. ↑ Kolata, Gina; Belluck, Pam (5 December 2018). "Why Are Scientists So Upset About the First Crispr Babies? - Only because a rogue researcher defied myriad scientific and ethical norms and guidelines. We break it down". The New York Times. Retrieved 5 December 2018.
  50. ↑ Li, Jing-ru; Walker, Simon; Nie, Jing-bao; Zhang, Xin-qing (January 2019). "Experiments that led to the first gene-edited babies: the ethical failings and the urgent need for better governance". Journal of Zhejiang University. Science. B. 20 (1): 32–38. doi:10.1631/jzus.B1800624. ISSN 1673-1581. PMC 6331330. PMID 30614228.
  51. ↑ Farr, Cristina (26 November 2018). "Experiments to gene-edit babies are 'criminally reckless,' says Stanford bio-ethicist". CNBC. Archived from the original on 27 November 2018.
  52. ↑ Greely, Henry T. (15 April 2019). "He Jiankui, embryo editing, CCR5, the London patient, and jumping to conclusions". Stat News. Retrieved 15 April 2019.
  53. ↑ Mozumder, Suman Guha. "Dr. Kiran Musunuru: On designer babies and genetic editing". IndiaAbroad.com. Retrieved 29 January 2021.
  54. ↑ Wang, Chen; Zhai, Xiaomei; Zhang, Xinqing; Li, Limin; Wang, Jianwei; Liu, De-pei (2019). "Gene-edited babies: Chinese Academy of Medical Sciences' response and action". The Lancet. 393 (10166): 25–26. doi:10.1016/S0140-6736(18)33080-0. PMID 30522918.
  55. ↑ Southern University of Science and Technology. "关于贺建奎副教授对人体胚胎进行基因编辑研究的情况声明(Information Statement on Associate Professor He Jiankui's Gene Editing Research on Human Embryos)". newshub.sustech.edu.cn. Retrieved 18 April 2022.
  56. ↑ Baltimore, David (28 November 2018). "Statement by the Organizing Committee of the Second International Summit on Human Genome Editing". National Academies. Retrieved 10 January 2023.
  57. ↑ C; Choi, Ice; Marchione, Marilynn (28 January 2019). "AP Exclusive: US Nobelist was told of gene-edited babies". AP NEWS. Retrieved 29 January 2019.
  58. ↑ Schmitz, Rob (5 February 2019). "Gene-Editing Scientist's 'Actions Are A Product Of Modern China'". NPR News. Retrieved 5 February 2019.
  59. ↑ Qiu, Jane (25 February 2019). "Chinese government funding may have been used for 'CRISPR babies' project, documents suggest". STAT News. Retrieved 1 March 2019.
  60. ↑ Chen, Angela (26 February 2019). "New documents suggest Chinese government helped fund the CRISPR babies experiment". The Verge. Retrieved 1 March 2019.
  61. 1 2 Belluz, Julia (4 March 2019). "CRISPR babies: the Chinese government may have known more than it let on - The latest developments in the gene-editing saga raise more questions than answers". Vox. Retrieved 4 March 2019.
  62. ↑ Jiang, Steven; Regan, Helen; Berlinger, Joshua (29 November 2018). "China suspends scientists who claim to have produced first gene-edited babies". CNN News. Retrieved 29 November 2018.
  63. ↑ Chen, Elsi; Mozur, Paul (28 December 2018). "Chinese Scientist Who Claimed to Make Genetically Edited Babies Is Kept Under Guard". The New York Times. Retrieved 29 December 2018.
  64. ↑ Senthilingam, Meera (7 January 2019). "Chinese scientist was told not to create world's first gene-edited babies". CNN News. Retrieved 21 January 2019.
  65. ↑ Ramzy, Austin; Wee, Sui-Lee (21 January 2019). "Scientist Who Edited Babies' Genes Is Likely to Face Charges in China". The New York Times. Retrieved 21 January 2019.
  66. ↑ Ramzy, Austin; Wee, Sui-Lee (21 January 2019). "Scientist Who Edited Babies' Genes Is Likely to Face Charges in China". The New York Times. ISSN 0362-4331. Retrieved 27 March 2022.
  67. ↑ The Beijing News (22 January 2019). "Guangdong Province identifies "gene edited babies" incident".
  68. ↑ Cyranoski, David (3 January 2020). "What CRISPR-baby prison sentences mean for research - Chinese court sends strong signal by punishing He Jiankui and two colleagues". Nature. 577 (7788): 154–155. doi:10.1038/d41586-020-00001-y. PMID 31911693.
  69. ↑ Normile, Dennis (30 December 2019). "Chinese scientist who produced genetically altered babies sentenced to 3 years in jail". Science. doi:10.1126/science.aba7347. S2CID 213806642.
  70. ↑ Cohen, Jon (21 March 2022). "As creator of 'CRISPR babies' nears release from prison, where does embryo editing stand?". Science. doi:10.1126/science.acx9233.
  71. ↑ LeMieux, Julianna (20 February 2019). "He Jiankui's Germline Editing Ethics Article Retracted by The CRISPR Journal". GEN - Genetic Engineering and Biotechnology News. Retrieved 16 January 2023.
  72. ↑ "Retraction of: Draft Ethical Principles for Therapeutic Assisted Reproductive Technologies by He, J et al., CRISPR J 2018; fast track. DOI: 10.1089/crispr.2018.0051". The CRISPR Journal. 2 (1): 65. 1 February 2019. doi:10.1089/crispr.2018.0051.retract. ISSN 2573-1599. PMC 6383508. PMID 30799870.
  73. ↑ LaMotte, Sandee (27 November 2018). "Rice professor under investigation for role in 'world's first gene-edited babies'". CNN News. Archived from the original on 27 November 2018. Retrieved 27 November 2018.
  74. ↑ Johnson, Carolyn Y. (31 December 2019). "Chinese scientist who claimed to create gene-edited babies sentenced to 3 years in prison". Washington Post. Retrieved 10 January 2020.
  75. ↑ Gill, Julian (11 April 2022). "Houston researcher with ties to 2018 gene-editing scandal no longer working at Rice University, officials say". Houston Chronicle. Retrieved 15 January 2023.
  76. ↑ Begley, Sharon (17 April 2019). "Stanford clears three faculty members of 'CRISPR babies' involvement". STAT. Retrieved 10 January 2020.
  77. ↑ "Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing". WHO. 14 December 2018. Retrieved 5 May 2022.
  78. ↑ "WHO expert advisory committee on developing global standards for governance and oversight of human genome editing: report of the first meeting". WHO. Retrieved 5 May 2022.
  79. ↑ "The World Health Organization Says No More Gene-Edited Babies". WIRED. 30 July 2019. Retrieved 26 November 2019.
  80. ↑ "WHO To Create Registry for Genetic Research". Voice of America. 29 August 2019. Retrieved 26 November 2019.
  81. ↑ "The WHO panel calls for registry of all human gene editing research". Reuters. 20 March 2019. Retrieved 26 November 2019.
  82. ↑ "WHO issues new recommendations on human genome editing for the advancement of public health". WHO. 12 July 2021. Retrieved 5 May 2022.
  83. ↑ Ledford, Heidi (12 July 2021). "WHO should lead on genome-editing policy, advisers say". Nature. doi:10.1038/d41586-021-01922-y. PMID 34253919. S2CID 235809263.
  84. 1 2 Song, Lingqiao; Joly, Yann (2021). "After He Jianku: China's biotechnology regulation reforms". Medical Law International. 21 (2): 174–192. doi:10.1177/0968533221993504. S2CID 235473692.
  85. ↑ "Legislative Review on Gene Editing in China". LawInfoChina.com. Retrieved 31 May 2023.
  86. 1 2 Ormond, Kelly E.; Mortlock, Douglas P.; Scholes, Derek T.; Bombard, Yvonne; Brody, Lawrence C.; Faucett, W. Andrew; Garrison, Nanibaa' A.; Hercher, Laura; et al. (2017). "Human Germline Genome Editing". American Journal of Human Genetics. 101 (2): 167–176. doi:10.1016/j.ajhg.2017.06.012. PMC 5544380. PMID 28777929.
  87. ↑ Coller, Barry S. (2019). "Ethics of Human Genome Editing". Annual Review of Medicine. 70 (1): 289–305. doi:10.1146/annurev-med-112717-094629. PMID 30691366. S2CID 59339196.
  88. ↑ Plaza Reyes, Alvaro; Lanner, Fredrik (2017). "Towards a CRISPR view of early human development: applications, limitations and ethical concerns of genome editing in human embryos". Development. 144 (1): 3–7. doi:10.1242/dev.139683. PMID 28049687. S2CID 14168067.
  89. ↑ Hershlag, Avner; Bristow, Sara L. (2018). "Editing the human genome: where ART and science intersect". Journal of Assisted Reproduction and Genetics. 35 (8): 1367–1370. doi:10.1007/s10815-018-1219-0. PMC 6086805. PMID 29882090.
  90. ↑ Ishii, Tetsuya (2017). "Germ line genome editing in clinics: the approaches, objectives and global society". Briefings in Functional Genomics. 16 (1): 46–56. doi:10.1093/bfgp/elv053. PMC 5291189. PMID 26615180.
  91. ↑ Lanphier, Edward; Urnov, Fyodor; Haecker, Sarah Ehlen; Werner, Michael; Smolenski, Joanna (2015). "Don't edit the human germ line". Nature. 519 (7544): 410–411. Bibcode:2015Natur.519..410L. doi:10.1038/519410a. PMID 25810189. S2CID 4471337.
  92. ↑ Rossant, Janet (2018). "Gene editing in human development: ethical concerns and practical applications". Development. 145 (16): dev150888. doi:10.1242/dev.150888. PMID 30045910. S2CID 51721841.
  93. ↑ Kaser, Daniel J.; Franasiak, Jason M. (2018). "Crossing the germline: CRISPR-Cas9 and our responsibility as reproductive endocrinology and infertility physicians". Journal of Assisted Reproduction and Genetics. 35 (3): 399–402. doi:10.1007/s10815-017-1075-3. PMC 5904053. PMID 29086321.
  94. ↑ Liu, Shuang (2020). "Legal reflections on the case of genome-edited babies". Global Health Research and Policy. 5: 24. doi:10.1186/s41256-020-00153-4. PMC 7222292. PMID 32435694.
  95. ↑ Drabiak, Katherine (2020). "The Nuffield Council's green light for genome editing human embryos defies fundamental human rights law". Bioethics. 34 (3): 223–227. doi:10.1111/bioe.12713. PMID 31943263. S2CID 210332359.
  96. ↑ Gyngell, Christopher; Bowman-Smart, Hilary; Savulescu, Julian (2019). "Moral reasons to edit the human genome: picking up from the Nuffield report". Journal of Medical Ethics. 45 (8): 514–523. doi:10.1136/medethics-2018-105084. PMC 6820147. PMID 30679191.
  97. ↑ Horton, Rachel; Lucassen, Anneke M. (2019). "The moral argument for heritable genome editing requires an inappropriately deterministic view of genetics". Journal of Medical Ethics. 45 (8): 526–527. doi:10.1136/medethics-2019-105390. PMID 30862707. S2CID 76666804.
  98. ↑ Chan, Sarah (2019). "Commentary on 'Moral reasons to edit the human genome': this is not the moral imperative we are looking for". Journal of Medical Ethics. 45 (8): 528–529. doi:10.1136/medethics-2018-105316. PMC 6820148. PMID 31455694.
  99. ↑ Saha, Krishanu; Sontheimer, Erik J.; Brooks, P. J.; Dwinell, Melinda R.; Gersbach, Charles A.; Liu, David R.; Murray, Stephen A.; Tsai, Shengdar Q.; et al. (2021). "The NIH Somatic Cell Genome Editing program". Nature. 592 (7853): 195–204. Bibcode:2021Natur.592..195S. doi:10.1038/s41586-021-03191-1. PMC 8026397. PMID 33828315.
  100. 1 2 Zhang, Laney (26 December 2018). "On Gene-Edited Babies: What Chinese Law Says". In Custodia Legis: Law Librarians of Congress. Retrieved 18 October 2020.
  101. ↑ Liao, Rita (26 November 2018). "Hospital in China denies links to world's first gene-edited babies". Techcrunch. Retrieved 8 January 2020.
  102. ↑ "Former ethics committee member of Shenzhen Hemei Women's and Pediatric Hospital: the signature of the examination application may be forged [Chinese]". wxn.qq.com. Retrieved 8 January 2020.
  103. ↑ Cyranoski, David (6 March 2019). "China to tighten rules on gene editing in humans". Nature. doi:10.1038/d41586-019-00773-y. S2CID 159086946.
  104. ↑ Krimsky, Sheldon (3 January 2019). "Ten ways in which He Jiankui violated ethics". Nature Biotechnology. 37 (1): 19–20. doi:10.1038/nbt.4337. PMID 30605150. S2CID 57376286.
  105. ↑ LeMieux, Julianna (20 February 2019). "He Jiankui's Germline Editing Ethics Article Retracted by The CRISPR Journal". GEN - Genetic Engineering and Biotechnology News. Retrieved 10 January 2020.
  106. ↑ "Retraction of: Draft Ethical Principles for Therapeutic Assisted Reproductive Technologies by He, J." The CRISPR Journal. 2 (1): 65. 21 February 2019. doi:10.1089/crispr.2018.0051.retract. PMC 6383508. PMID 30799870.
  107. 1 2 3 Rothschild, Jodie (2020). "Ethical considerations of gene editing and genetic selection". Journal of General and Family Medicine. 21 (3): 37–47. doi:10.1002/jgf2.321. PMC 7260159. PMID 32489755.
  108. ↑ Begley, Sharon (27 November 2018). "He took a crash course in bioethics, then created CRISPR babies". STAT. Retrieved 10 January 2020.
  109. ↑ Shaw, David (3 January 2020). "The Consent Form in the Chinese CRISPR Study: In Search of Ethical Gene Editing". Journal of Bioethical Inquiry. 17 (1): 5–10. doi:10.1007/s11673-019-09953-x. PMC 7223878. PMID 31900853.
  110. 1 2 Getz, LJ; Dellaire, G (1 October 2020). "Back to Basics: Application of the Principles of Bioethics to Heritable Genome Interventions". Science and Engineering Ethics. 26 (5): 2735–48. doi:10.1007/s11948-020-00226-0. ISSN 1471-5546. PMID 32524426. S2CID 255428830.
  111. 1 2 3 Lei, Ruipeng; Qiu, Renzong (2020). "Ethical and regulatory issues in human gene editing: Chinese perspective". Biotechnology and Applied Biochemistry. 67 (6): 880–891. doi:10.1002/bab.2032. ISSN 0885-4513. PMID 33011985. S2CID 222165039.
  112. 1 2 3 4 5 Protections (OHRP), Office for Human Research (28 January 2010). "The Belmont Report". HHS.gov. Retrieved 27 February 2023.
  113. ↑ Beauchamp, Tom L. (2019). Principles of biomedical ethics. James F. Childress. New York, NY. ISBN 978-0-19-064087-3. OCLC 1114281405.{{cite book}}: CS1 maint: location missing publisher (link)
  114. 1 2 3 Ouagrham-Gormley, SB; Vogel, KM (3 July 2020). "Follow the money: What the sources of Jiankui He's funding reveal about what Beijing authorities knew about illegal CRISPR babies, and when they knew it". Bulletin of the Atomic Scientists. 76 (4): 192–99. Bibcode:2020BuAtS..76d.192O. doi:10.1080/00963402.2020.1780726. ISSN 0096-3402. S2CID 221059420.
  115. ↑ Zhang, F.; Wen, Y; Guo, X (15 September 2014). "CRISPR/Cas9 for genome editing: progress, implications and challenges". Human Molecular Genetics. 23 (R1): R40–R46. doi:10.1093/hmg/ddu125. ISSN 0964-6906. PMID 24651067.
  116. 1 2 "健康产业网". cmw-gov.cn. Retrieved 27 February 2023.
  117. ↑ Barmania, Fatima; Pepper, Michael S. (2013). "C-C chemokine receptor type five (CCR5): An emerging target for the control of HIV infection". Applied & Translational Genomics. 2 (1): 3–16. doi:10.1016/j.atg.2013.05.004. PMC 5133339. PMID 27942440.
  118. 1 2 Rautenbach, Anandi; Williams, Aurelia A. (2020). "Metabolomics as an Approach to Characterise the Contrasting Roles of CCR5 in the Presence and Absence of Disease". International Journal of Molecular Sciences. 21 (4): 1472. doi:10.3390/ijms21041472. PMC 7073144. PMID 32098198.
  119. ↑ Smoleń-Dzirba, J; Rosińska, M; Janiec, J; Beniowski, M; Cycoń, M; Bratosiewicz-Wąsik, J; Wąsik, TJ (2017). "HIV-1 Infection in Persons Homozygous for CCR5-Δ32 Allele: The Next Case and the Review". AIDS Reviews. 19 (4): 219–230. PMID 28534889.
  120. ↑ Trecarichi, Enrico M; Tumbarello, Mario; Donati, Katleen; Tamburrini, Enrica; Cauda, Roberto; Brahe, Christina; Tiziano, Francesco D (2006). "Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals". AIDS Research and Therapy. 3 (1): 22. doi:10.1186/1742-6405-3-22. PMC 1592103. PMID 16999868.
  121. ↑ Lederman, Michael M.; Pike, Earl (20 November 2017). "Ten Years HIV Free: An Interview with "The Berlin Patient," Timothy Ray Brown". Pathogens and Immunity. 2 (3): 422–430. doi:10.20411/pai.v2i3.226. PMC 5708572. PMID 29202113.
  122. 1 2 Wang, Haoyi; Yang, Hui (2019). "Gene-edited babies: What went wrong and what could go wrong". PLOS Biology. 17 (4): e3000224. doi:10.1371/journal.pbio.3000224. PMC 6490877. PMID 31039144.
  123. 1 2 Ryder, Sean P. (2018). "#CRISPRbabies: Notes on a Scandal". The CRISPR Journal. 1 (6): 355–357. doi:10.1089/crispr.2018.29039.spr. PMC 6345105. PMID 30687814.
  124. ↑ Cohen, Jon (28 November 2018). "'I feel an obligation to be balanced.' Noted biologist comes to defense of gene editing babies". Science. doi:10.1126/science.aaw2120. S2CID 150047968. Retrieved 10 January 2020.
  125. ↑ Regalado, Antonio (21 February 2019). "China's CRISPR twins might have had their brains inadvertently enhanced - New research suggests that a controversial gene-editing experiment to make children resistant to HIV may also have enhanced their ability to learn and form memories". MIT Technology Review. Retrieved 21 February 2019.
  126. ↑ Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K.; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha (20 December 2016). "CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory". eLife. 5. doi:10.7554/eLife.20985. ISSN 2050-084X. PMC 5213777. PMID 27996938.
  127. ↑ Carmichael, S. Thomas; Shohami, Esther; Silva, Alcino J.; Bornstein, Natan M.; Katz, Noomi; Silva, Tawnie K.; Huang, Shan; Zhou, Miou; Kesner, Efrat L. (21 February 2019). "CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury". Cell. 176 (5): 1143–1157.e13. doi:10.1016/j.cell.2019.01.044. ISSN 0092-8674. PMC 7259116. PMID 30794775.
  128. ↑ Society and Ethics Research Wellcome Genome Campus (3 December 2018), 28 Nov 2018 - International Summit on Human Genome Editing - He Jiankui presentation and Q&A, retrieved 22 February 2019
  129. ↑ Gallagher, James (3 June 2019). "He Jiankui: Baby gene experiment 'foolish and dangerous'". BBC News. Retrieved 3 June 2019.
  130. ↑ Stein, Rob (3 June 2019). "2 Chinese Babies With Edited Genes May Face Higher Risk Of Premature Death". NPR News. Retrieved 3 June 2019.
  131. ↑ Wei, Xinzhu; Nielsen, Rasmus (3 June 2019). "CCR5-∆32 is deleterious in the homozygous state in humans". Nature Medicine. 25 (6): 909–910. doi:10.1038/s41591-019-0459-6. PMC 6613792. PMID 31160814.
  132. ↑ Sample, Ian (3 June 2019). "Gene mutation meant to protect from HIV 'raises risk of early death'". The Guardian. Retrieved 9 January 2020.
  133. ↑ Daley, Jason (5 June 2019). "China's 'CRISPR Babies' May Be More Likely to Die Young". Smithsonian Magazine. Retrieved 9 January 2020.
  134. ↑ Greshko, Michael (3 June 2019). "Error undermines finding of health risks in first gene-edited babies". Science. Archived from the original on 4 June 2019. Retrieved 9 January 2020.
  135. ↑ Wei, Xinzhu; Nielsen, Rasmus (8 October 2019). "Retraction Note: CCR5-∆32 is deleterious in the homozygous state in humans". Nature Medicine. 25 (11): 1796. doi:10.1038/s41591-019-0637-6. PMC 7184837. PMID 31595084.
  136. ↑ Normile, Dennis (26 November 2018). "CRISPR bombshell: Chinese researcher claims to have created gene-edited twins". Science. doi:10.1126/science.aaw1839. S2CID 92802132. Retrieved 10 January 2020.
  137. ↑ Magowan, Jakki (9 December 2019). "Unpublished paper surfaces about the Chinese genome-edited babies". Bionews.org.uk. Retrieved 10 January 2020.
  138. ↑ Regalado, Antonio (3 December 2019). "Why the paper on the CRISPR babies stayed secret for so long". MIT Technology Review. Retrieved 10 January 2020.
  139. ↑ Cloer, Dan (2019). "Interview: Genetically Modified Babies: An Insider's View". Vision.org. Retrieved 10 January 2020.
  140. ↑ Musunuru, Kiran (3 December 2019). "Opinion: We need to know what happened to CRISPR twins Lulu and Nana - The unpublished research paper by He Jiankui about the creation of the babies shows proof of attempted gene editing gone awry". MIT Technology Review. Retrieved 3 December 2019.
  141. ↑ Dey, R.; Pillai, B. (2015). "Cell-based gene therapy against HIV". Gene Therapy. 22 (11): 851–855. doi:10.1038/gt.2015.58. PMID 26079406. S2CID 21626148.
  142. ↑ Kay, Mark A.; Walker, Bruce D. (6 March 2014). "Engineering cellular resistance to HIV". The New England Journal of Medicine. 370 (10): 968–969. doi:10.1056/NEJMe1400593. PMID 24597871.
  143. ↑ Tebas, Pablo; Stein, David; Tang, Winson W.; Frank, Ian; Wang, Shelley Q.; Lee, Gary; Spratt, S. Kaye; Surosky, Richard T.; et al. (6 March 2014). "Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV". New England Journal of Medicine. 370 (10): 901–910. doi:10.1056/NEJMoa1300662. PMC 4084652. PMID 24597865.
  144. ↑ Yang, Hui; Wang, Haoyi; Shivalila, Chikdu S.; Cheng, Albert W.; Shi, Linyu; Jaenisch, Rudolf (2013). "One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas-mediated genome engineering". Cell. 154 (6): 1370–1379. doi:10.1016/j.cell.2013.08.022. PMC 3961003. PMID 23992847.
  145. ↑ Li, Wei; Teng, Fei; Li, Tianda; Zhou, Qi (2013). "Simultaneous generation and germline transmission of multiple gene mutations in rat using CRISPR-Cas systems". Nature Biotechnology. 31 (8): 684–686. doi:10.1038/nbt.2652. PMID 23929337. S2CID 205278783.
  146. ↑ Niu, Yuyu; Shen, Bin; Cui, Yiqiang; Chen, Yongchang; Wang, Jianying; Wang, Lei; Kang, Yu; Zhao, Xiaoyang; Si, Wei; Li, Wei; Xiang, Andy Peng (2014). "Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos". Cell. 156 (4): 836–843. doi:10.1016/j.cell.2014.01.027. PMID 24486104. S2CID 612983.
  147. ↑ Cohen, Jon (31 July 2019). "China's CRISPR push in animals promises better meat, novel therapies, and pig organs for people". Science. doi:10.1126/science.aay9194. S2CID 201213025.
  148. ↑ Wang, Shuang; Ren, Shuaiwei; Bai, Raoxian; Xiao, Puhao; Zhou, Qin; Zhou, Yin; Zhou, Zhigang; Niu, Yuyu; Ji, Weizhi; Chen, Yongchang (2018). "No off-target mutations in functional genome regions of a CRISPR/Cas9-generated monkey model of muscular dystrophy". The Journal of Biological Chemistry. 293 (30): 11654–11658. doi:10.1074/jbc.AC118.004404. PMC 6066302. PMID 29941452.
  149. ↑ Zhang, Weiqi; Wan, Haifeng; Feng, Guihai; Qu, Jing; Wang, Jiaqiang; Jing, Yaobin; Ren, Ruotong; Liu, Zunpeng; Zhang, Linlin; Chen, Zhiguo; Wang, Shuyan (2018). "SIRT6 deficiency results in developmental retardation in cynomolgus monkeys". Nature. 560 (7720): 661–665. Bibcode:2018Natur.560..661Z. doi:10.1038/s41586-018-0437-z. PMID 30135584. S2CID 52068504.
  150. ↑ Liu, Zhen; Cai, Yijun; Wang, Yan; Nie, Yanhong; Zhang, Chenchen; Xu, Yuting; Zhang, Xiaotong; Lu, Yong; Wang, Zhanyang; Poo, Muming; Sun, Qiang (24 January 2018). "Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer". Cell. 172 (4): 881–887.e7. doi:10.1016/j.cell.2018.01.020. PMID 29395327.
  151. ↑ Cyranoski, David (25 January 2018). "First monkeys cloned with technique that made Dolly the sheep". Nature. 553 (7689): 387–388. Bibcode:2018Natur.553..387C. doi:10.1038/d41586-018-01027-z. PMID 29368720. S2CID 4391482.
  152. ↑ Mandelbaum, Ryan F. (23 January 2019). "China's Latest Cloned-Monkey Experiment Is an Ethical Mess". Gizmodo. Retrieved 24 January 2019.
  153. ↑ Kang, Yu; Chu, Chu; Wang, Fang; Niu, Yuyu (2019). "CRISPR/Cas9-mediated genome editing in nonhuman primates". Disease Models & Mechanisms. 12 (10): dmm039982. doi:10.1242/dmm.039982. PMC 6826017. PMID 31636095.
  154. ↑ Offord, Catherine (3 September 2018). "US Companies Launch CRISPR Clinical Trial". The Scientist Magazine. Retrieved 11 January 2020.
  155. ↑ "CRISPR Therapeutics and Vertex Announce Positive Safety and Efficacy Data From First Two Patients Treated With Investigational CRISPR/Cas9 Gene-Editing Therapy CTX001® for Severe Hemoglobinopathies | Vertex Pharmaceuticals". investors.vrtx.com. Vertex. 19 November 2019. Retrieved 19 September 2021.
  156. 1 2 Ledford, Heidi (2020). "CRISPR gene therapy shows promise against blood diseases". Nature. 588 (7838): 383. Bibcode:2020Natur.588..383L. doi:10.1038/d41586-020-03476-x. PMID 33299166. S2CID 228087119.
  157. ↑ Frangoul, Haydar; Altshuler, David; Cappellini, M. Domenica; Chen, Yi-Shan; Domm, Jennifer; Eustace, Brenda K.; Foell, Juergen; de la Fuente, Josu; Grupp, Stephan; Handgretinger, Rupert; Ho, Tony W. (21 January 2021). "CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia". The New England Journal of Medicine. 384 (3): 252–260. doi:10.1056/NEJMoa2031054. ISSN 1533-4406. PMID 33283989. S2CID 227521558.
  158. ↑ Esrick, Erica B.; Lehmann, Leslie E.; Biffi, Alessandra; Achebe, Maureen; Brendel, Christian; Ciuculescu, Marioara F.; Daley, Heather; MacKinnon, Brenda; Morris, Emily; Federico, Amy; Abriss, Daniela (21 January 2021). "Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease". The New England Journal of Medicine. 384 (3): 205–215. doi:10.1056/NEJMoa2029392. PMC 7962145. PMID 33283990.
  159. ↑ Cyranoski, David (10 June 2019). "Russian biologist plans more CRISPR-edited babies". Nature. 570 (7760): 145–146. Bibcode:2019Natur.570..145C. doi:10.1038/d41586-019-01770-x. PMID 31186565.
  160. ↑ Cyranoski, David (18 October 2019). "Russian 'CRISPR-baby' scientist has started editing genes in human eggs with goal of altering deaf gene". Nature. 574 (7779): 465–466. Bibcode:2019Natur.574..465C. doi:10.1038/d41586-019-03018-0. PMID 31641261.
  161. ↑ "Early Results from First-In-U.S. Trial of CRISPR-Edited Immune Cells for Cancer Patients Suggest Safety of Approach". Penn Medicine News. 6 November 2019. Retrieved 19 September 2021.
  162. 1 2 "CRISPR-Edited Immune Cells Can Survive and Thrive After Infusion into Cancer Patients - Penn Medicine". Penn Medicine News. 6 February 2020. Retrieved 19 September 2021.
  163. ↑ "NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells)". ClinicalTrials.gov. U.S. Department of Health and Human Services. 12 October 2018. Retrieved 19 September 2021.
  164. ↑ Stadtmauer, Edward A.; Fraietta, Joseph A.; Davis, Megan M.; Cohen, Adam D.; Weber, Kristy L.; Lancaster, Eric; Mangan, Patricia A.; Kulikovskaya, Irina; Gupta, Minnal; Chen, Fang; Tian, Lifeng (2020). "CRISPR-engineered T cells in patients with refractory cancer". Science. 367 (6481): eaba7365 (1–12). doi:10.1126/science.aba7365. PMID 32029687. S2CID 211048335.
  165. ↑ Hamilton, Jennifer R.; Doudna, Jennifer A. (28 February 2020). "Knocking out barriers to engineered cell activity". Science. 367 (6481): 976–977. Bibcode:2020Sci...367..976H. doi:10.1126/science.aba9844. OSTI 1633261. PMID 32029685. S2CID 211050477.
  166. ↑ Mo, Feiyan; Heslop, Helen E.; Mamonkin, Maksim (2020). "CRISPR-Edited Immune Effectors: The End of the Beginning". Molecular Therapy. 28 (4): 995–996. doi:10.1016/j.ymthe.2020.03.009. PMC 7132620. PMID 32203679.
  167. ↑ Couzin-Frankel, Jennifer (6 February 2020). "Cutting-edge CRISPR gene editing appears safe in three cancer patients". Science. doi:10.1126/science.abb1990. S2CID 213644900.
  168. ↑ Lu, You; Xue, Jianxin; Deng, Tao; Zhou, Xiaojuan; Yu, Kun; Deng, Lei; Huang, Meijuan; Yi, Xin; Liang, Maozhi; Wang, Yu; Shen, Haige (2020). "Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer". Nature Medicine. 26 (5): 732–740. doi:10.1038/s41591-020-0840-5. PMID 32341578. S2CID 216559642.
  169. ↑ Lacey, Simon F.; Fraietta, Joseph A. (2020). "First Trial of CRISPR-Edited T cells in Lung Cancer". Trends in Molecular Medicine. 26 (8): 713–715. doi:10.1016/j.molmed.2020.06.001. PMID 32536469. S2CID 219704051.
  170. ↑ He, Shenghui (2020). "The first human trial of CRISPR-based cell therapy clears safety concerns as new treatment for late-stage lung cancer". Signal Transduction and Targeted Therapy. 5 (1): 168. doi:10.1038/s41392-020-00283-8. PMC 7447629. PMID 32843656.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.