Advances in base editing with an emphasis on an AAV-based strategy.

ABSTRACT

The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based base editors have been developed for precisely installing point mutations in genomes with high efficiency. Two editing systems of cytosine base editors (CBEs) and adenine base editors (ABEs) have been developed for conversion of C.G-to-T.A and A.T-to-G.C, respectively, showing the prominence in genomic DNA correction and mutation. Here, we summarize recent optimized approaches in improving base editors, including the evolution of Cas proteins, the choice of deamination enzymes, modification on linker length, base-editor expression, and addition of functional domains. Specifically, in this paper we highlight a strategy of split-intein mediated base-editor reconstitution for its adeno-associated virus (AAV) delivery. The purpose of this article is to offer readers with a better understanding of AAV-mediated base editors, and facilitate them to use this tool in in vivo experiments and potential clinical applications.