Catalyst Biosciences, Inc.
GENE THERAPY FOR HEMOPHILIA B WITH A CHIMERIC AAV CAPSID VECTOR ENCODING MODIFIED FACTOR IX POLYPEPTIDES

Abstract:

AAV vectors that encode a modified Factor IX (FIX) polypeptide for gene therapy for treatment of hemophilia B are provided. The modified FIX polypeptide has increased potency compared to the wild-type FIX polypeptide. The nucleic acid encoding the modified FIX polypeptide includes a portion of an intron. The AAV vectors were generated and selected to infect islet cells, but were found to effectively transduce hepatocytes upon systemic administration, and to express high levels of FIX polypeptide. Relatively low doses of the AAV vectors can be administered to achieve a therapeutic effect. The gene therapy treatment can result in normal or near normal coagulation pharmacokinetics and normal levels of FIX, or mild hemophilia B. Combining an AAV vector with improved properties for transducing hepatocytes, and modified FIX polypeptides with enhanced potency, improves transgene expression and effectively lowers the viral dose needed to achieve therapeutically relevant FIX activity levels.