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CRISPR-Pass: Gene Rescue of Nonsense Mutations Using Adenine Base Editors.

ABSTRACT: A nonsense mutation is a substitutive mutation in a DNA sequence that causes a premature termination during translation and produces stalled proteins, resulting in dysfunction of a gene. Although it usually induces severe genetic disorders, there are no definite methods for inducing read through of premature termination codons (PTCs). Here, we present a targeted tool for bypassing PTCs, named CRISPR-pass, that uses CRISPR-mediated adenine base editors. CRISPR-pass, which should be applicable to 95.5% of clinically significant nonsense mutations in the ClinVar database, rescues protein synthesis in patient-derived fibroblasts, suggesting potential clinical utility.

SUBMITTER: Lee C

PROVIDER: S-EPMC6698196 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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CRISPR-Pass: Gene Rescue of Nonsense Mutations Using Adenine Base Editors.

Lee Choongil C Hyun Jo Dong D Hwang Gue-Ho GH Yu Jihyeon J Kim Jin Hyoung JH Park Se-Eun SE Kim Jin-Soo JS Kim Jeong Hun JH Bae Sangsu S

Molecular therapy : the journal of the American Society of Gene Therapy 20190524 8

A nonsense mutation is a substitutive mutation in a DNA sequence that causes a premature termination during translation and produces stalled proteins, resulting in dysfunction of a gene. Although it usually induces severe genetic disorders, there are no definite methods for inducing read through of premature termination codons (PTCs). Here, we present a targeted tool for bypassing PTCs, named CRISPR-pass, that uses CRISPR-mediated adenine base editors. CRISPR-pass, which should be applicable to ...[more]

PMID: 31164261

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