CRISPR Start-Loss: A Novel and Practical Alternative for Gene Silencing through Base-Editing-Induced Start Codon Mutations

CRISPR-Cas9-mediated gene knockout and base-editing-associated induction of STOP codons (iSTOP) have been widely used to exterminate the function of a coding gene, while they have been reported to exhibit side effects. In this study, we propose a novel and practical alternative method referred to as...

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Main Authors: Siyu Chen (Author), Wanhua Xie (Author), Zhiquan Liu (Author), Huanhuan Shan (Author), Mao Chen (Author), Yuning Song (Author), Hao Yu (Author), Liangxue Lai (Author), Zhanjun Li (Author)
Format: Book
Published: Elsevier, 2020-09-01T00:00:00Z.
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Summary:CRISPR-Cas9-mediated gene knockout and base-editing-associated induction of STOP codons (iSTOP) have been widely used to exterminate the function of a coding gene, while they have been reported to exhibit side effects. In this study, we propose a novel and practical alternative method referred to as CRISPR Start-Loss (CRISPR-SL), which eliminates gene expression by utilizing both adenine base editors (ABEs) and cytidine base editors (CBEs) to disrupt the initiation codon (ATG). CRISPR-SL has been verified to be a feasible strategy on the cellular and embryonic levels (mean editing efficiencies up to 30.67% and 73.50%, respectively) and in two rabbit models mimicking Otc deficiency (Otc gene) and long hair economic traits (Fgf5 gene).
Item Description:2162-2531
10.1016/j.omtn.2020.07.037