Novel factor VIII variants with a modified furin cleavage site improve the efficacy of gene therapy for hemophilia A.

ABSTRACT: Essentials Factor (F) VIII is an inefficiently expressed protein. Furin deletion FVIII variants were purified and characterized using in vitro and in vivo assays. These minimally modified novel FVIII variants have enhanced function. These variants provide a strategy for increasing FVIII expression in hemophilia A gene therapy.

Summary

Background The major challenge for developing gene-based therapies for hemophilia A is that human factor VIII (hFVIII) has intrinsic properties that result in inefficient biosynthesis. During intracellular processing, hFVIII is predominantly cleaved at a paired basic amino acid cleaving enzyme (PACE) or furin cleavage site to yield a heterodimer that is the major form of secreted protein. Previous studies with B-domain-deleted (BDD) canine FVIII and hF

SUBMITTER: Nguyen GN 

PROVIDER: S-EPMC5280213 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature