Adenine base editors induce off-target structure variations in mouse embryos and primary human T cells.

ABSTRACT:

Background

The safety of CRISPR-based gene editing methods is of the utmost priority in clinical applications. Previous studies have reported that Cas9 cleavage induced frequent aneuploidy in primary human T cells, but whether cleavage-mediated editing of base editors would generate off-target structure variations remains unknown. Here, we investigate the potential off-target structural variations associated with CRISPR/Cas9, ABE, and CBE editing in mouse embryos and primary human T cells by whole-genome sequencing and single-cell RNA-seq analyses.

Results

The results show that both Cas9 and ABE generate off-target structural variations (SVs) in mouse embryos, while CBE induces rare SVs. In addition, off-target large deletions are detected in 32.74% of primary human T cells

SUBMITTER: Wu L 

PROVIDER: S-EPMC11552398 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature