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Non-viral Intron Knockins Enable Simplified and Flexible Targeting of Endogenous Genes

Roth, T. L.; Lu, J.; McClellan, A.; Takacsi-Nagy, O.; Satpathy, A. L.

2024-03-05 bioengineering
10.1101/2024.03.05.582227 bioRxiv
Show abstract

Targeting new genetic material to endogenous genes has opened diverse therapeutic and research applications, but current exon-based targeting methods have limited integration sites and are compatible only with complex or harsh selection methods. We present non-viral intron targeting, integrating large synthetic exons into endogenous introns to increase targeting flexibility and simplify selection of successfully edited cells. Engineered control of large synthetic exons splicing behavior further generalizes cell and gene therapy applications of non-viral intron knockins.

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