Approximately one in 5000 males in human population suffers from coagulation disorder, hemophilia A. This disease is primarily caused by deficiency in the factor VIII gene located in the X-chromosome and is difficult to treat by conventional medicine. Current treatment of hemophilia A by intravenous infusion of factor VIII concentrates is very costly and has a potential side effect of developing inhibitors. Gene therapy, on the other hand, can potentially prevent these limitations of current treatments. Although recombinant adeno-associated virus (rAAV) vectors are promising for deliver factor VIII gene, applying AAV vector technology to Hemophilia A lagged behind other genetic diseases because of this size constraint (limited to ~5kb). To improve factor VIII gene delivery utilizing rAAV vectors, we have developed novel engineered factor VIII molecules for use in both dual vectors and single vector strategy.
The specific aims for this proposal are: 1). To develop a Factor VIII heavy chain molecule efficient for secretion;2). To develop and characterize a novel mini factor VIII gene for rAAV delivery;3). To analyze immune responses against the engineered factor VIII transgene products. The success of this proposal may lead to a clinical trial of hemophilia A using AAV vectors.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL084381-06
Application #
8208029
Study Section
Gene and Drug Delivery Systems Study Section (GDD)
Program Officer
Link, Rebecca P
Project Start
2008-01-01
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2013-12-31
Support Year
6
Fiscal Year
2012
Total Cost
$417,285
Indirect Cost
$139,095
Name
Temple University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
057123192
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
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