Discovery and engineering of AiEvo2, a novel Cas12a nuclease for human gene editing applications.

ABSTRACT: The precision of gene editing technology is critical to creating safe and effective therapies for treating human disease. While the programmability of CRISPR-Cas systems has allowed for rapid innovation of new gene editing techniques, the off-target activity of these enzymes has hampered clinical development for novel therapeutics. Here, we report the identification and characterization of a novel CRISPR-Cas12a enzyme from Acinetobacter indicus (AiCas12a). We engineer the nuclease (termed AiEvo2) for increased specificity, protospacer adjacent motif recognition, and efficacy on a variety of human clinical targets. AiEvo2 is highly precise and able to efficiently discriminate between normal and disease-causing alleles in Huntington's patient-derived cells by taking advantage of a single nuc

SUBMITTER: Sharrar A 

PROVIDER: S-EPMC10877636 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature