Journal Article

Amplified genome editing by in vivo editor production

Qiu, Longhui, Kang, Min Hyung, Wu, Jamie L Y, Rosas-Rivera, Daniel, Gogna, Shaan, Li, Zhongmei, Wasko, Kevin M, Ngo, Wayne, Hooks, Mason T, Doudna, Jennifer A, Zeng, Jingkun

2026

Overview

Genome editing enzymes have vast therapeutic potential. However, achieving sufficient delivery remains a major challenge, because editing machinery is confined to the subset of transfectable cells in a tissue. Here, we tested the possibility that genome editing could be amplified by programming transfected cells to produce and transfer editing enzymes in lipid vesicles to neighboring cells. Our data show that this NANoparticle-Induced Transfer of Enzyme (NANITE) strategy tripled editing efficiency in cultured cells relative to non-spreading controls. Furthermore, a single intravenous injection of the NANITE plasmid into mice induced ~3-fold higher levels of liver editing at the locus relative to non-spreading controls, with corresponding reductions in serum transthyretin levels. Amplifying therapeutic enzymes offers a nonviral and non-infectious strategy to overcome low delivery efficiencies and reduce effective dose requirements.

• Publisher: Cold Spring Harbor Laboratory Preprints