The current PPG is focused on three different preclinical animal models pertinent to developing gene therapy treatment strategies for hemophilia. These animal models are critical towards developing translational strategies for hemophilia gene therapy. The Animal Core will serve as an integral component of the UNC PPG. Activities to support PPG members will include colony breeding, maintenance and genotyping as well as vector construction, administration and characterization in the context of with the ultimate goal of developing clinically relevant gene therapy modalities. Each ofthe mouse strains required by Projects 1 through 4 will be bred and maintained by the Animal Core to facilitate rapid and efficient dissemination to individual projects. Project 3 is focused on evaluating l.A. prevention of hemarthropathy in dogs. All canine model studies will be carried out at the Frances Owen Blood Research Lab and Canine model facility at UNC. Project 4 is focused on developing a non-human primate model of hemophilia B that can be utilized for the study of factor IX deficiency as well as allow for the preclinicaltesting of therapeutic approaches for the treatment of patients with factor IX deficiency. All primate model studies will be carried out at the primate facility at UC Davis.

Public Health Relevance

The current PPG is focused on three different preclinical animal models pertinent to developing gene therapy treatment strategies for hemophilia. These animal models are critical towards developing translational strategies for hemophilia gene therapy. The Animal Core will serve as an integral component of the UNC PPG.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL112761-02
Application #
8616797
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
2
Fiscal Year
2014
Total Cost
$233,848
Indirect Cost
$56,160
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Xiao, Ping-Jie; Mitchell, Angela M; Huang, Lu et al. (2016) Disruption of Microtubules Post-Virus Entry Enhances Adeno-Associated Virus Vector Transduction. Hum Gene Ther 27:309-24
Wang, M; Sun, J; Crosby, A et al. (2016) Direct interaction of human serum proteins with AAV virions to enhance AAV transduction: immediate impact on clinical applications. Gene Ther :
Li, Chengwen; Wu, Shuqing; Albright, Blake et al. (2016) Development of Patient-specific AAV Vectors After Neutralizing Antibody Selection for Enhanced Muscle Gene Transfer. Mol Ther 24:53-65
Berry, Garrett E; Asokan, Aravind (2016) Chemical Modulation of Endocytic Sorting Augments Adeno-associated Viral Transduction. J Biol Chem 291:939-47
Berry, Garrett Edward; Asokan, Aravind (2016) Cellular transduction mechanisms of adeno-associated viral vectors. Curr Opin Virol 21:54-60
Nelson, Christopher E; Hakim, Chady H; Ousterout, David G et al. (2016) In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science 351:403-7
Murlidharan, Giridhar; Crowther, Andrew; Reardon, Rebecca A et al. (2016) Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain. JCI Insight 1:e88034
Schreiber, Claire A; Sakuma, Toshie; Izumiya, Yoshihiro et al. (2015) An siRNA Screen Identifies the U2 snRNP Spliceosome as a Host Restriction Factor for Recombinant Adeno-associated Viruses. PLoS Pathog 11:e1005082
Goodrich, L R; Grieger, J C; Phillips, J N et al. (2015) scAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy. Gene Ther 22:536-45
Hastie, Eric; Samulski, R Jude (2015) Recombinant adeno-associated virus vectors in the treatment of rare diseases. Expert Opin Orphan Drugs 3:675-689

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