Value Proposition

AAV has become one of the leading gene delivery vectors in clinical development. Gene therapy using recombinant AAV has been demonstrated to be safe and well-tolerated in virtually every clinical setting in which it has been used. To date nearly 100 clinical trials are testing the safety and efficacy of AAV based vectors in the US alone. In fact, the FDA recently approved the first AAV based gene therapy in the United States, voretigene neparvovec (LUXTURNA), for the treatment of RPE65 mutation-associated retinal dystrophy. Additionally, aliogene tiparvovec (Glybera), an AAV based treatment for lipoprotein deficiency (LPLD) was approved in 2012 in Europe. It is expected that additional AAV approved vectors will follow.


Technical Summary

Mayo Clinic researchers in the Department of Molecular Medicine have identified the U2 snRNP sliceosome complex as a novel host factor that restricts AAV based vector transgene expression. They have shown that disruption of PHD finger-like domain protein 5A (PHF5A), a U2 snRNP-associated protein, selectively enhanced AAV mediated transgene expression. Furthermore, pharmacological inhibition of PHF5A associated proteins such as SF3B1 and U2AF1 strongly increased AAV mediated transgene expression in clinically relevant cell types. The researchers have shown that using U2 inhibitors improves AAV vector transduction efficiency in vitro. In addition, U2 inhibiting compounds were found to enhance viral transduction and transgene expression in vivo as well.

Developmental Stage

In vitro data has been obtained and proof-of-concept has been demonstrated.


Link to Technical Brief

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