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CRISPR-Cas9 DNA Base-Editing and Prime-Editing

Kantor, Ariel, McClements, Michelle, MacLaren, Robert·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21176240PMC PMC7503568
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Abstract

Many genetic diseases and undesirable traits are due to base-pair alterations in genomic DNA. Base-editing, the newest evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas-based technologies, can directly install point-mutations in cellular DNA without inducing a double-strand DNA break (DSB). Two classes of DNA base-editors have been described thus far, cytosine base-editors (CBEs) and adenine base-editors (ABEs). Recently, prime-editing (PE) has further expanded the CRISPR-base-edit toolkit to all twelve possible transition and transversion mutations, as well as small insertion or deletion mutations. Safe and efficient delivery of editing systems to target cells is one of the most paramount and challenging components for the therapeutic success of BEs. Due to its broad tropism, well-studied serotypes, and reduced immunogenicity, adeno-associated vector (AAV) has emerged as the leading platform for viral delivery of genome editing agents, including DNA-base-editors. In this review, we describe the development of various base-editors, assess their technical advantages and limitations, and discuss their therapeutic potential to treat debilitating human diseases.

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  • CRISPR Cas9, Base and Prime editing, PASTE, and other versions of gene editing are becoming cost effective and may become mainstream services accessible to the general public.

    “CRISPR Cas9, Base and Prime editing, Programmable Addition via Site‐specific Targeting Elements (PASTE), and other versions of gene editing are becoming cost effective and may cause the trajectory of these technologies to become mainstream services that the general public can access easily. 48 , 50 , 51”

    From Three Tiers to biological escape velocity: The quest to outwit aging (2022) · cites this paper as [50]

    The Introduction and Conclusions discuss CRISPR-Cas9, base editing, and prime editing and describe their therapeutic potential. They do not support the claims that these technologies are becoming cost-effective or may become easily accessible mainstream services for the general public; the passages found also do not discuss PASTE. The Conclusions instead emphasize that safe, effective delivery remains a major hurdle. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Prime editing promises higher precision by circumventing double-strand breaks and enabling a greater range of edits than base editing.

    “prime editing that promise higher precision by circumventing the introduction of double-strand breaks (DSBs) and the subsequent error rate of the DSB repair mechanisms while enabling a greater range of possible edits than base editing (Kantor et al. 2020).”

    From Initial heritable genome editing: mapping a responsible pathway from basic research to the clinic (2023) · cites this paper as Kantor et al. 2020

  • CRISPR/Cas base editor and prime editor systems do not produce double-strand breaks (DSBs), which reduces the possibility of indels compared with conventional Cas-9.

    “The CRISPR/Cas-base editor and prime editor system do not produce DSB, which reduces the possibility of indels that are different from conventional Cas-9.38”

    From Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing (2021) · cites this paper as [38]

  • The adenine base editor (ABE) uses adenosine deaminase fused to dCas-9 to correct the base-pair change from adenosine (A) to guanosine (G).

    “The ABE uses adenosine deaminase fused to dCas-9 to correct the base-pair change from adenosine (A) to guanosine (G).38”

    From Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing (2021) · cites this paper as [38]

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Metadata

Authors
Kantor, A., McClements, M., & MacLaren, R.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-08-28
Volume
21
Issue
17
Pages
6240
ISSN
1422-0067
DOI
10.3390/ijms21176240
PMC
PMC7503568
Cited by
462
References
32
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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