Poly(beta-amino ester)-Based Nanoparticles Enable Nonviral Delivery of Base Editors for Targeted Tumor Gene Editing.

Abstract

Base editing is an emerging genome editing technology with the advantages of precise base corrections, no double-strand DNA breaks, and no need for templates, which provides an alternative treatment option for tumors with point mutations. However, effective nonviral delivery systems for base editors (BEs) are still limited. Herein, a series of poly(beta-amino esters) (PBAEs) with varying backbones, side chains, and end caps were synthesized to deliver plasmids of BEs and sgRNA. Efficient transfection and base editing were achieved in HEK-293T-sEGFP and U87-MG-sEGFP reporter cell lines by using lead PBAEs, which were superior to PEI and lipo3k. A single intratumor injection of PBAE/pDNA nanoparticles induced the robust conversion of stopped-EGFP into EGFP in mice bearing xenograft glioma tumors, indicating successful gene editing by ABEmax-NG. Overall, these results demonstrated that PBAEs can efficiently deliver BEs for tumor gene editing both in vitro and in vivo.