Abstract
Base editors (BEs) are widely used in precise gene editing due to their simplicity and versatility. However, their efficiencies are hindered by various obstacles. Considering the chromatin microenvironment as a possible obstacle, here, we demonstrate a further development of the proxy-clustered regularly interspaced short palindromic repeats strategy, termed Proxy-BE, to increase gene editing efficiency. Specifically, a nuclease-dead Cas9 (dCas9) was bound to the sequence about 20-30 base pair away from the target site, potentially improving access to the DNA and, thus, providing a better editing microenvironment for base editors. Our findings confirm that nuclease-dead Streptococcuspyogenes Cas9 can assist the base editors SaKKH-BE3 and dCpf1-BE to double their canonical base editing efficiency. This work provides a new approach to enhance base editing, extending its scope for biological research and gene therapy.
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