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Harnessing RNA-based DNA repair pathways for targeted gene editing

Huynh, N.; Kwon, S.; McMurrough, T. A.; Loedige, K. W.; Tavassoli, M.; Weijuan, S.; Quin, H.; Luu, K.; Dharni, B.; Haydaychuk, O.; Stead, B. E.; Edgell, D.

2024-04-10 molecular biology
10.1101/2024.04.09.588775 bioRxiv
Show abstract

Recent studies have revealed a role for RNA in the repair of DNA double-strand breaks. Here, we show that the asymmetric DNA overhangs generated by the small TevSaCas9 dual nuclease informs a simple and robust editing strategy in human cells whereby Pol{theta} and Rad52 are recruited to repair the double-strand break. The 2-nt, 3 DNA overhang generated by the I-TevI nuclease domain of TevSaCas9 hybridizes with the 3 end of a co-localized repair template guide RNA to specifically license repair. Substitutions that destabilize the repair duplex reduce editing efficiency. Targeted RNA-templated repair (rep-editing) harnesses cellular RNA-based DNA repair pathways to introduce precise nucleotide edits, deletions and insertions in human cells with high efficiency and fidelity independent of co-delivered repair functions. The small size of TevSaCas9 and RNA repair template offers delivery advantages over size-constrained or multi-component editing systems.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.