Computationally designed liver-specific transcriptional cis-regulatory modules and hyper-functional factor IX improve liver-targeted gene therapy for hemophilia B. Vrije Universiteit Brussel
The development of the next-generation gene therapy vectors for hemophilia requires the use of lower and thus potentially safer vector doses, while augmenting their therapeutic efficacy. We have identified hepatocyte-specific transcriptional cis-regulatory modules (CRMs) using a computational strategy that increased factor IX (FIX) levels 11 to 15-fold. Vector efficacy could be enhanced by combining these hepatocyte-specific CRMs with a ...