Precision BioSciences Inc (DTIL)

[jondoeuk]

Given the effectiveness of a single shRNA targeting approach, the obvious next step would be to investigate targeting of multiple genes with shRNA.

CYAD previously demonstrated concurrent knockdown of up to four different genes (multiplexing) in T-cells with their first-gen shRNA scaffold. Even though this allowed the knockdown of multiple targets and was successful in terms of target knockdown, there was a reduction in transduction efficacy (with a viral vector).

This was variable between the duplex and triplex shRNA constructs, but were uniformly low when compared to the single shRNA construct. Therefore, they have been working on ways to engineer a second generation of shRNA scaffold that could enable consistent expression of duplexed and triplexed shRNAs, while improving transduction, therefore making it suitable for future clinical application.