Amplified genome editing by in vivo editor production

Ngo, W.; Rosas-Rivera, D.; Wasko, K. M.; Qiu, L.; Kang, M. H.; Gogna, S.; Zeng, J.; Hooks, M. T.; Wu, J. L. Y.; Li, Z.; Doudna, J. A.

doi:10.64898/2026.01.13.699115

bioRxiv · 10.64898/2026.01.13.699115

Amplified genome editing by in vivo editor production

Ngo, W.·Rosas-Rivera, D.·Wasko, K. M.·Qiu, L.·Kang, M. H.·Gogna, S.·Zeng, J.·Hooks, M. T.·Wu, J. L. Y.·Li, Z.·Doudna, J. A.

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Abstract

Genome editing enzymes have vast therapeutic potential. However, achieving sufficient delivery in vivo 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 in vivo by enabling transfected cells to transfer editing enzymes to neighboring cells. Our data show that this NANoparticle-Induced Transfer of Enzyme (NANITE) strategy quadrupled editing efficiency in cultured cells relative to non-spreading controls. A single intravenous injection of the NANITE plasmid into mice induced ~3-fold higher levels of liver editing at the transthyretin (Ttr) locus relative to non-spreading controls, with corresponding reductions in serum TTR levels. Spreading therapeutic enzymes offers a nonviral and non-infectious strategy to boost therapeutic effects after delivery.

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Ngo, W., Rosas-Rivera, D., Wasko, K. M., Qiu, L., Kang, M. H., Gogna, S., Zeng, J., Hooks, M. T., Wu, J. L. Y., Li, Z., Doudna, J. A.. 2026-01-13. Amplified genome editing by in vivo editor production. https://doi.org/10.64898/2026.01.13.699115

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