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Cited by 1,459CRISPR and Genetic EngineeringRNA regulation and diseaseCAR-T cell therapy research

The next generation of CRISPR–Cas technologies and applications

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Pickar-Oliver, Adrian, Gersbach, Charles A.·2019·Nature Reviews Molecular Cell Biology
DOI 10.1038/s41580-019-0131-5PMC PMC7079207
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Abstract

The prokaryote-derived CRISPR-Cas genome editing systems have transformed our ability to manipulate, detect, image and annotate specific DNA and RNA sequences in living cells of diverse species. The ease of use and robustness of this technology have revolutionized genome editing for research ranging from fundamental science to translational medicine. Initial successes have inspired efforts to discover new systems for targeting and manipulating nucleic acids, including those from Cas9, Cas12, Cascade and Cas13 orthologues. Genome editing by CRISPR-Cas can utilize non-homologous end joining and homology-directed repair for DNA repair, as well as single-base editing enzymes. In addition to targeting DNA, CRISPR-Cas-based RNA-targeting tools are being developed for research, medicine and diagnostics. Nuclease-inactive and RNA-targeting Cas proteins have been fused to a plethora of effector proteins to regulate gene expression, epigenetic modifications and chromatin interactions. Collectively, the new advances are considerably improving our understanding of biological processes and are propelling CRISPR-Cas-based tools towards clinical use in gene and cell therapies.

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  • Several Cas variants, such as Cas12 and Cas13, have been developed to enhance DNA cleavage and expand genome editing versatility.

    “In recent years, several Cas variants, such as Cas12 and Cas13, have been developed to enhance DNA cleavage and expand genome editing versatility [7,8].”

    From Precise CRISPR/Cas9 and Cas12 Correction Using Lipoplexes in Retinal Models Derived from Patients with Inherited Retinal Dystrophies (2026) · cites this paper as [7]

    The 'Broader targeting capacity' section says Cas12a cuts DNA and that engineered variants improve its genome-editing activity and targeting range. But the 'Cas13' section describes Cas13 as an RNA-targeting nuclease, not a variant developed to enhance DNA cleavage. The claim therefore overextends a DNA-cleavage benefit to Cas13. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Pickar-Oliver, A., & Gersbach, C. A.
Affiliations
Duke University (US)
Corresponding author
Gersbach, Charles A.
ORCID
Gersbach, Charles A.
Venue
Nature Reviews Molecular Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2019-05-30
Volume
20
Issue
8
Pages
490-507
ISSN
  • 1471-0072 (ISSN-L)
  • 1471-0080
DOI
10.1038/s41580-019-0131-5
PMC
PMC7079207
OpenAlex
W2947777875
Cited by
1,459
References
43
Citations by year
2026: 128 · 2025: 189 · 2024: 211 · 2023: 228 · 2022: 253 · 2021: 222 · 2020: 196 · 2019: 30
FWCI
15.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Molecular Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (UG3TR002142)
  • National Institute on Drug Abuse (R33DA041878, R01DA036865)
  • National Human Genome Research Institute (U01HG007900, UM1HG009428)
  • National Institute of General Medical Sciences (R41GM119914)
  • National Institute of Allergy and Infectious Diseases (R41AI136755)
  • National Institute of Neurological Disorders and Stroke (R21NS103007)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR066527, R01AR069085)
  • National Center for Advancing Translational Sciences
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
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
Keywords
CRISPR-Cas, genome editing, Cas9, Cas12, cascades, Cas13, single-base editing, epigenetic regulation, gene therapy, cell therapy, DNA repair, homology-directed repair, non-homologous end joining, CRISPR-based diagnostics
MeSH terms
Gene Editing, RNA, Guide, CRISPR-Cas Systems, Animals, Endonucleases, Humans, Genetic Therapy, RNA, Guide, Kinetoplastida, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems

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