Molecular Therapy
Volume 27, Issue 8, 7 August 2019, Pages 1364-1371
Journal home page for Molecular Therapy

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

https://doi.org/10.1016/j.ymthe.2019.05.013Get rights and content
Under a Creative Commons license
open access

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.

Keywords

CRISPR-Cas9
base editing
nonsense mutation
stop codon read through
premature termination codon

Cited by (0)

8

These authors contributed equally to this work.