Cited by 609CRISPR and Genetic EngineeringRNA regulation and diseaseVirus-based gene therapy research

Past, present, and future of CRISPR genome editing technologies

Open access
Pacesa, Martin, Pelea, Oana, Jinek, Martin·2024·Cell

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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Crossref · 10.1016/j.cell.2024.01.042

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345 of 345 references verified0 citation errors · 0 not checkable

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  • Chemical modifications involving 2′-O-methyl or 2′-fluoro nucleotides and phosphorothioate linkages in the gRNA enhance both the specificity of Cas9 and the stability of the gRNA.

    “Additionally, chemical modifications involving 2′-O-methyl or 2′-fluoro nucleotides and phosphorothioate linkages in the gRNA have proven to be effective strategies for enhancing both the specificity of Cas9 and the stability of the gRNA (Martin et al., 2024).”
  • Each high-fidelity variant is not universally acceptable and possesses certain limitations.

    “Nevertheless, each of the high-fidelity variants is not universally acceptable and possesses certain limitations (Martin et al., 2024).”
  • Cas12a does not require a tracrRNA for activation and is potentially exploited for multiplexed editing.

    “The Cas12a does not require a tracrRNA for activation and is potentially exploited for multiplexed editing (Martin et al., 2024).”
  • First-generation CRISPR-based gene editing tools face challenges including specificity, targeting scope, dependency on endogenous DSB repair mechanisms, absence of efficient delivery methods, lack of effective vectors, rigidity of cell or organisms, and off-target activity.

    “The first-generation CRISPR-based gene editing tools face several challenges, including specificity, targeting scope, dependency on endogenous DSB repair mechanisms, absence of efficient delivery methods, lack of effective vectors and rigidity of cell or organisms, off-target activity, etc. (Kadam et al., 2018; Martin et al., 2024).”
  • Base editing options have been expanded beyond ABE and CBE and cover A-to-C, A-to-Y and C-to-G edits.

    “Further base editing option has been expanded beyond ABE and CBE and covers A-to-C, A-to-Y and C-to-G (Martin et al., 2024) edits.”

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Authors
Pacesa, M., Pelea, O., & Jinek, M.
Affiliations
University of Zurich (CH)
Venue
Cell
Publisher
Elsevier BV
Published
2024-02
Volume
187
Issue
5
Pages
1076-1100
ISSN
0092-8674 (ISSN-L)
OpenAlex
W4392303996
Cited by
609
References
345
Citations by year
2026: 266 · 2025: 262 · 2024: 81
FWCI
24.90
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords
CRISPR gene editing, genome editing, CRISPR/Cas9, gene therapy, genetic disorders
MeSH terms
Gene Editing, Biological Science Disciplines, Humans, Technology, Genetic Therapy, CRISPR-Cas Systems

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