Adeno-Associated Viral Vector Delivery of Optimized Human Factor VIII Achieves Therapeutic Factor VIII Levels in Non-Human Primates

The impact of minimally oversized adeno-associated viral vectors encoding human factor VIII on vector potency in vivo

Recombinant adeno-associated viral (rAAV) vectors containing oversized genomes provide transgene expression despite low efficiency packaging of complete genomes. Here, we characterized the properties of oversized rAAV2/8 vectors (up to 5.4 kb) encoding human factor VIII (FVIII) under the transcriptional control of three liver promoters. All vectors provided sustained production of active FVIII ...

Bioengineered coagulation factor VIII enables long-term correction of murine hemophilia A following liver-directed adeno-associated viral vector delivery

Clinical data support the feasibility and safety of adeno-associated viral (AAV) vectors in gene therapy applications. Despite several clinical trials of AAV-based gene transfer for hemophilia B, a unique set of obstacles impede the development of a similar approach for hemophilia A. These include (i) the size of the factor VIII (fVIII) transgene, (ii) humoral immune responses to fVIII, (iii) i...

FACTOR V AND VIII INHIBITOR IN PATIENTS WITH COMBINED FACTOR V AND VIII DEFICIENCY

Patients with coagulation factor(s) deficiency who use coagulation therapy are susceptible to forming inhibitors against coagulation factor(s). In this survey we detected factor V and VIII inhibitor in ten patients with combined deficiency of factors V and VIII from north east of Iran (Khorassan province). It was revealed in our survey that eight patients had both factor V and factor VIII i...

Bacterial Expression and Purification of C1C2 Domain of Human Factor VIII

With the aim of the production of human factor VIII antigen and its corresponding antibody an epitope coding fragment of the light-chain of hFVIII, fused to a His6-tag, was isolated and over-expressed in Escherichia coli. The over-expressed hFVIII-epitope containing peptide was confirmed by its reaction with a rabbit serum directed against native hFVIII as well as antiHis6-tag antibody. An expr...

Expression of Biologically Active Recombinant B-Domain-Deleted Human Factor VIII in Mammalian Cells