Author Correction: Human germline genome editing

Lea, Rebecca A.; Niakan, Kathy K.

doi:10.1038/s41556-019-0451-x

Cited by 3 publications

(3 citation statements)

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“…However, nonnegligible frequencies of editingassociated large deletions have been reported after the use of the Cas9 D10A nickase in mESCs (14) and prime editing in early mouse embryos (43). By contrast, while proof-of-principle studies suggest that base editors could be used to repair diseaseassociated mutations in human embryos, further refinements to reduce the likelihood of unexpected conversion patterns and high rates of off-target edits would be of benefit (2). There are too few studies to date using repair templates.…”

Section: Discussionmentioning

confidence: 99%

“…genome editing | CRISPR-Cas9 | human embryo | segmental aneuploidy | loss of heterozygosity C lustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR associated 9 (Cas9) genome editing is not only an indispensable molecular biology technique (1) but also has enormous therapeutic potential as a tool to correct disease-causing mutations (2). Genome editing of human embryos or germ cells to produce heritable changes has the potential to reduce the burden of genetic disease, and its use in this context is currently a topic of international discussions centered around ethics, safety, and efficiency (3,4).…”

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confidence: 99%

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Frequent loss of heterozygosity in CRISPR-Cas9–edited early human embryos

Alanis-Lobato

Zohren

McCarthy

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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160

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CRISPR-Cas9 genome editing is a promising technique for clinical applications, such as the correction of disease-associated alleles in somatic cells. The use of this approach has also been discussed in the context of heritable editing of the human germ line. However, studies assessing gene correction in early human embryos report low efficiency of mutation repair, high rates of mosaicism, and the possibility of unintended editing outcomes that may have pathologic consequences. We developed computational pipelines to assess single-cell genomics and transcriptomics datasets from OCT4 (POU5F1) CRISPR-Cas9–targeted and control human preimplantation embryos. This allowed us to evaluate on-target mutations that would be missed by more conventional genotyping techniques. We observed loss of heterozygosity in edited cells that spanned regions beyond the POU5F1 on-target locus, as well as segmental loss and gain of chromosome 6, on which the POU5F1 gene is located. Unintended genome editing outcomes were present in ∼16% of the human embryo cells analyzed and spanned 4–20 kb. Our observations are consistent with recent findings indicating complexity at on-target sites following CRISPR-Cas9 genome editing. Our work underscores the importance of further basic research to assess the safety of genome editing techniques in human embryos, which will inform debates about the potential clinical use of this technology.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Frequent loss of heterozygosity in CRISPR-Cas9–edited early human embryos

Alanis-Lobato

Zohren

McCarthy

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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160

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“…23 One of the problems induced by application of technology in the field of genetic editing in the case of human embryos or germ cells is the possibility of determining the appearance of hereditary changes in the human genome, intergenerational effects that occur in the case of using these modified cells for a pregnancy that will be carried to term. [24][25][26] The technology applied for editing the germline genome affects in vitro embryos used in research and the hereditary genome which is useable in medical practice, respectively in reproductive medicine; but in ethical analysis, it is necessary to approach the 2 aspects differently, with the distinct realization of the analysis. https://doi.org/10.1089/crispr.2020.0082.…”

Section: Introductionmentioning

confidence: 99%

Advances in Genetic Editing of the Human Embryo

Astărăstoae

Ioan

Rogozea

et al. 2023

American Journal of Therapeutics

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Background: Genetic engineering has allowed a major development of research in this field, with specialists attempting to edit the human genome, after the successful editing of the genomes of plants and animals. However, human gene editing technologies are at the center of ethical debates around the world.Areas of Uncertainty: Ethical concerns about genetic editing of the human embryo raise several issues that can be viewed through the prism of optimism and reluctance leading to a number of recommendations regarding the acceptance of what may soon become a reality.Data Sources: A literature search was conducted through PubMed, MEDLINE, Plus, Scopus, and Web of Science (2015-2022) using combinations of keywords, including: human genome or gene editing plus ethics.Ethics and Therapeutic Advances: Gene therapy is seen by researchers as a way to solve congenital diseases, multifactorial diseases in general or specific diseases such as cystic fibrosis, muscular dystrophy, or can increase resistance to HIV infection. Genome editing technologies, germline gene editing, clustered regularly interspaced short palindromic repeats gene editing technology, technologies such as zinc finger nucleases are not only advanced gene therapies that require solving technical problems, but also techniques that require complex and complete analysis of ethical problems. Genetic engineering raises many ethical concerns such as: safety concerns especially the risk of off-target effects; autonomy of the individual-with the limitation of the future generations to consent for an intervention over their genome; social justice-keeping in mind the costs of the procedures and their availability to the general population. Discussions can go further from questions such as "How can we do this?" to questions such as "Should we do this?" or "Is society ready to accept this technology and is it able to manage it rationally?" Conclusions: The ethics of biomedical research should be based on global dialogue, on the involvement of experts and the public, to achieve a broad social consensus. The fundamental review of the ethics of genetics is a desire and an opportunity of the current period.

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CRISPR/Cas9 ribonucleoprotein-mediated genome and epigenome editing in mammalian cells

Bloomer

Khirallah

et al. 2022

Advanced Drug Delivery Reviews

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Author Correction: Human germline genome editing

Cited by 3 publications

References 0 publications

Frequent loss of heterozygosity in CRISPR-Cas9–edited early human embryos

Frequent loss of heterozygosity in CRISPR-Cas9–edited early human embryos

Advances in Genetic Editing of the Human Embryo

CRISPR/Cas9 ribonucleoprotein-mediated genome and epigenome editing in mammalian cells

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