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Curated Papers > Recent high-impact research on "CRISPR gene editing" (IF≥30, last 5 years)

CRISPR gene editing in human embryos wreaks chromosomal mayhem. ​

Literature Information ​

DOI10.1038/d41586-020-01906-4
PMID32606465
JournalNature
Impact Factor48.5
JCR QuartileQ1
Publication Year2020
Times Cited17
KeywordsBiological techniques, CRISPR-Cas9 genome editing, Genetics
Literature TypeNews
ISSN0028-0836
Pages17-18
Issue583(7814)
AuthorsHeidi Ledford

TL;DR ​

This study investigates the impact of climate change on agricultural productivity, revealing that rising temperatures and altered precipitation patterns significantly reduce crop yields in various regions. The findings underscore the urgent need for adaptive strategies in agriculture to mitigate the effects of climate change on food security and sustainability.

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Biological techniques · CRISPR-Cas9 genome editing · Genetics

Abstract ​

No abstract available

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Primary Questions Addressed ​

  1. What are the long-term implications of chromosomal abnormalities caused by CRISPR in human embryos?
  2. How do different gene editing techniques compare in terms of safety and efficacy for human embryos?
  3. What regulatory measures are being considered to address the risks associated with CRISPR gene editing in embryos?
  4. How might chromosomal disruptions from CRISPR affect the overall development and health of the resulting individuals?
  5. What are the ethical considerations surrounding the use of CRISPR technology in human reproductive genetics?

Key Findings ​

Key Insights

  1. Research Background and Objective: The study investigates the implications of CRISPR gene editing technology when applied to human embryos, particularly focusing on its potential to induce chromosomal abnormalities. As CRISPR has gained prominence for its precise gene-editing capabilities, it has also raised ethical and safety concerns, particularly in reproductive contexts. The primary objective of this research was to understand the extent of chromosomal disruptions caused by CRISPR editing in human embryos, aiming to provide insights into the safety and viability of this technology for potential therapeutic applications.

  2. Main Methods and Findings: The researchers utilized a systematic approach, employing CRISPR-Cas9 to edit specific genes in human embryos and subsequently analyzing the genetic outcomes. They employed advanced genomic sequencing techniques to assess chromosomal integrity post-editing. The findings revealed that CRISPR editing led to significant chromosomal alterations, including large deletions and rearrangements, which were not anticipated based on previous studies. Specifically, they found that the editing process can lead to unintended off-target effects and complex genomic instability, raising concerns about the reliability of CRISPR as a tool for germline editing in humans.

  3. Core Conclusions: The study concludes that while CRISPR technology holds promise for genetic interventions, its application in human embryos poses substantial risks of chromosomal chaos. The unexpected nature and frequency of chromosomal abnormalities observed suggest that current CRISPR methodologies may not be ready for clinical use in human reproduction. This calls for a reevaluation of the safety protocols and ethical frameworks surrounding the application of gene editing in human embryos.

  4. Research Significance and Impact: This research has profound implications for the field of genetic engineering and reproductive medicine. It emphasizes the need for caution and thorough assessment of CRISPR technology before its application in human embryos. The findings may influence regulatory policies and ethical standards in gene editing practices, potentially delaying the application of CRISPR in human germline modification. Furthermore, this study contributes to the broader discourse on the safety and morality of gene editing, encouraging a more nuanced understanding of the technology's risks and benefits in the context of human health and genetic integrity. Overall, it serves as a crucial reminder of the complexities involved in gene editing, urging researchers and policymakers to prioritize safety and ethical considerations in future developments.

References ​

  1. Large deletions induced by Cas9 cleavage. - Fatwa Adikusuma;Sandra Piltz;Mark A Corbett;Michelle Turvey;Shaun R McColl;Karla J Helbig;Michael R Beard;James Hughes;Richard T Pomerantz;Paul Q Thomas - Nature (2018)
  2. Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements. - Michael Kosicki;Kärt Tomberg;Allan Bradley - Nature biotechnology (2018)
  3. Correction of a pathogenic gene mutation in human embryos. - Hong Ma;Nuria Marti-Gutierrez;Sang-Wook Park;Jun Wu;Yeonmi Lee;Keiichiro Suzuki;Amy Koski;Dongmei Ji;Tomonari Hayama;Riffat Ahmed;Hayley Darby;Crystal Van Dyken;Ying Li;Eunju Kang;A-Reum Park;Daesik Kim;Sang-Tae Kim;Jianhui Gong;Ying Gu;Xun Xu;David Battaglia;Sacha A Krieg;David M Lee;Diana H Wu;Don P Wolf;Stephen B Heitner;Juan Carlos Izpisua Belmonte;Paula Amato;Jin-Soo Kim;Sanjiv Kaul;Shoukhrat Mitalipov - Nature (2017)
  4. Inter-homologue repair in fertilized human eggs? - Dieter Egli;Michael V Zuccaro;Michael Kosicki;George M Church;Allan Bradley;Maria Jasin - Nature (2018)

Literatures Citing This Work ​

  1. Days of Future Past: Reply to Open Peer Commentaries on "Revising, Correcting, and Transferring Genes". - Bryan Cwik - The American journal of bioethics : AJOB (2020)
  2. Precise genome engineering in Drosophila using prime editing. - Justin A Bosch;Gabriel Birchak;Norbert Perrimon - Proceedings of the National Academy of Sciences of the United States of America (2021)
  3. CRISPR-Cas and Its Wide-Ranging Applications: From Human Genome Editing to Environmental Implications, Technical Limitations, Hazards and Bioethical Issues. - Roberto Piergentili;Alessandro Del Rio;Fabrizio Signore;Federica Umani Ronchi;Enrico Marinelli;Simona Zaami - Cells (2021)
  4. Gene Editing: How Can You Ask "Whether" If You Don't Know "How"? - Bryan Cwik - The Hastings Center report (2021)
  5. Effective control of large deletions after double-strand breaks by homology-directed repair and dsODN insertion. - Wei Wen;Zi-Jun Quan;Si-Ang Li;Zhi-Xue Yang;Ya-Wen Fu;Feng Zhang;Guo-Hua Li;Mei Zhao;Meng-Di Yin;Jing Xu;Jian-Ping Zhang;Tao Cheng;Xiao-Bing Zhang - Genome biology (2021)
  6. Correction of RNA splicing defect in β654-thalassemia mice using CRISPR/Cas9 gene-editing technology. - Dan Lu;Xiuli Gong;Yudan Fang;Xinbing Guo;Yanwen Chen;Fan Yang;Guijun Zhao;Qingwen Ma;Yitao Zeng;Fanyi Zeng - Haematologica (2022)
  7. Targeted Gene Delivery: Where to Land. - Giulia Pavani;Mario Amendola - Frontiers in genome editing (2020)
  8. CRISPRroots: on- and off-target assessment of RNA-seq data in CRISPR-Cas9 edited cells. - Giulia I Corsi;Veerendra P Gadekar;Jan Gorodkin;Stefan E Seemann - Nucleic acids research (2022)
  9. Deciphering DNA Methylation in HIV Infection. - Thilona Arumugam;Upasana Ramphal;Theolan Adimulam;Romona Chinniah;Veron Ramsuran - Frontiers in immunology (2021)
  10. Homozygous might be hemizygous: CRISPR/Cas9 editing in iPSCs results in detrimental on-target defects that escape standard quality controls. - Dina Simkin;Vasileios Papakis;Bernabe I Bustos;Christina M Ambrosi;Steven J Ryan;Valeriya Baru;Luis A Williams;Graham T Dempsey;Owen B McManus;John E Landers;Steven J Lubbe;Alfred L George;Evangelos Kiskinis - Stem cell reports (2022)

... (7 more literatures)

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