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Past, present, and future of CRISPR genome editing technologies.

Literature Information

DOI10.1016/j.cell.2024.01.042
PMID38428389
JournalCell
Impact Factor42.5
JCR QuartileQ1
Publication Year2024
Times Cited117
KeywordsCRISPR gene editing, gene therapy, biotechnology
Literature TypeJournal Article, Review
ISSN0092-8674
Pages1076-1100
Issue187(5)
AuthorsMartin Pacesa, Oana Pelea, Martin Jinek

TL;DR

This review highlights the transformative impact of CRISPR-based genome editing technologies in life sciences and medicine, emphasizing their efficiency and programmability while addressing current limitations and recent technological innovations. It also explores the landscape of gene editing applications in human health, discussing potential future developments that could enhance therapeutic interventions for genetic diseases.

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CRISPR gene editing · gene therapy · biotechnology

Abstract

Genome editing has been a transformative force in the life sciences and human medicine, offering unprecedented opportunities to dissect complex biological processes and treat the underlying causes of many genetic diseases. CRISPR-based technologies, with their remarkable efficiency and easy programmability, stand at the forefront of this revolution. In this Review, we discuss the current state of CRISPR gene editing technologies in both research and therapy, highlighting limitations that constrain them and the technological innovations that have been developed in recent years to address them. Additionally, we examine and summarize the current landscape of gene editing applications in the context of human health and therapeutics. Finally, we outline potential future developments that could shape gene editing technologies and their applications in the coming years.

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Primary Questions Addressed

  1. What are the specific limitations of current CRISPR technologies that researchers are actively working to overcome?
  2. How do the advancements in CRISPR gene editing technologies compare to other genome editing methods like TALENs and ZFNs?
  3. In what ways can CRISPR technology be integrated into personalized medicine approaches for treating genetic diseases?
  4. What ethical considerations are emerging as CRISPR technologies advance in both research and clinical applications?
  5. How might future innovations in CRISPR technology impact the field of gene therapy and its accessibility to patients?

Key Findings

Key Insights

  1. Research Background and Purpose
    The research detailed in the review explores the evolution and current status of CRISPR genome editing technologies, which have revolutionized life sciences and medical research. The primary aim is to examine how CRISPR has enabled scientists to understand complex biological processes and address genetic diseases at their source. The review also seeks to identify existing limitations of CRISPR technologies and highlight recent innovations aimed at overcoming these challenges.

  2. Key Methods and Findings
    The authors provide a comprehensive overview of CRISPR gene editing, detailing its applications in both laboratory research and therapeutic contexts. They discuss various CRISPR systems, particularly CRISPR-Cas9, emphasizing its efficiency and programmability as key advantages. The review identifies critical limitations such as off-target effects, delivery challenges, and ethical concerns that hinder the broader application of CRISPR in clinical settings. Additionally, the authors highlight recent technological innovations, including improved delivery mechanisms, enhanced specificity, and alternative CRISPR systems (such as CRISPR-Cas12 and CRISPR-Cas13) that promise to expand the capabilities and safety of gene editing.

  3. Core Conclusions
    The review concludes that while CRISPR technologies have made significant strides in both research and therapeutic applications, there are still considerable hurdles to overcome. Innovations in the field are rapidly evolving, suggesting a potential for more precise, efficient, and safer genome editing tools in the near future. The authors emphasize the importance of continued research to address current limitations and the ethical implications of gene editing technologies.

  4. Research Significance and Impact
    The significance of this research lies in its comprehensive evaluation of CRISPR technologies, which are pivotal in advancing genetic research and therapeutic interventions. By summarizing the current landscape and future prospects of CRISPR applications, the review provides valuable insights for researchers, clinicians, and policymakers. The anticipated advancements in CRISPR technologies could lead to transformative therapies for genetic diseases, enhance our understanding of biological systems, and raise important ethical discussions regarding the implications of editing the human genome. This positions CRISPR as a cornerstone of future biomedical research and a key player in the development of personalized medicine.

Literatures Citing This Work

  1. Functional CRISPR screens in T cells reveal new opportunities for cancer immunotherapies. - Minghua Xiang;Huayi Li;Yuanyuan Zhan;Ding Ma;Qinglei Gao;Yong Fang - Molecular cancer (2024)
  2. Precise Gene Knock-In Tools with Minimized Risk of DSBs: A Trend for Gene Manipulation. - Yongfeng Liu;Jianping Kong;Gongyu Liu;Zhaoxing Li;Yibei Xiao - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
  3. Revolutionizing Playing with Skeleton Atoms: Molecular Editing Surgery in Medicinal Chemistry. - Amgad M Rabie - Mini reviews in medicinal chemistry (2025)
  4. Programmable RNA-guided enzymes for next-generation genome editing. - Connor J Tou;Benjamin P Kleinstiver - Nature (2024)
  5. Regulation of Precise DNA Repair by Nuclear Actin Polymerization: A Chance for Improving Gene Therapy? - Xiubin He;Cord Brakebusch - Cells (2024)
  6. The Role of Endothelial Cell Mitophagy in Age-Related Cardiovascular Diseases. - Quancheng Han;Yiding Yu;Xiujuan Liu;Yonghong Guo;Jingle Shi;Yitao Xue;Yan Li - Aging and disease (2024)
  7. Enhancing homology-directed repair efficiency with HDR-boosting modular ssDNA donor. - Ying-Ying Jin;Peng Zhang;Le-Le Liu;Xiang Zhao;Xiao-Qing Hu;Si-Zhe Liu;Ze-Kun Li;Qian Liu;Jian-Qiao Wang;De-Long Hao;Zhu-Qin Zhang;Hou-Zao Chen;De-Pei Liu - Nature communications (2024)
  8. Editing microbes to mitigate enteric methane emissions in livestock. - Faheem Ahmed Khan;Azhar Ali;Di Wu;Chunjie Huang;Hamza Zulfiqar;Muhammad Ali;Bilal Ahmed;Muhammad Rizwan Yousaf;Ezi Masdia Putri;Windu Negara;Muhammad Imran;Nuruliarizki Shinta Pandupuspitasari - World journal of microbiology & biotechnology (2024)
  9. Next-generation CRISPR technology for genome, epigenome and mitochondrial editing. - Cia-Hin Lau;Qing-Le Liang;Haibao Zhu - Transgenic research (2024)
  10. On RNA-programmable gene modulation as a versatile set of principles targeting muscular dystrophies. - Sabrina Capelletti;Sofía C García Soto;Manuel A F V Gonçalves - Molecular therapy : the journal of the American Society of Gene Therapy (2024)

... (107 more literatures)


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