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 #
1P01HL112761-01A1
Application #
8460292
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-02-08
Budget End
2014-01-31
Support Year
1
Fiscal Year
2013
Total Cost
$326,800
Indirect Cost
$111,800
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Shen, Shen; Berry, Garrett E; Castellanos Rivera, Ruth M et al. (2015) Functional analysis of the putative integrin recognition motif on adeno-associated virus 9. J Biol Chem 290:1496-504
Suwanmanee, Thipparat; Hu, Genlin; Gui, Tong et al. (2014) Integration-deficient lentiviral vectors expressing codon-optimized R338L human FIX restore normal hemostasis in Hemophilia B mice. Mol Ther 22:567-74
Lau, A G; Sun, J; Hannah, W B et al. (2014) Joint bleeding in factor VIII deficient mice causes an acute loss of trabecular bone and calcification of joint soft tissues which is prevented with aggressive factor replacement. Haemophilia 20:716-22
Nicolson, Sarah C; Samulski, R Jude (2014) Recombinant adeno-associated virus utilizes host cell nuclear import machinery to enter the nucleus. J Virol 88:4132-44
Hemphill, Daniel D; McIlwraith, C Wayne; Samulski, R Jude et al. (2014) Adeno-associated viral vectors show serotype specific transduction of equine joint tissue explants and cultured monolayers. Sci Rep 4:5861
Mitchell, Angela M; Hirsch, Matthew L; Li, Chengwen et al. (2014) Promyelocytic leukemia protein is a cell-intrinsic factor inhibiting parvovirus DNA replication. J Virol 88:925-36
Shen, Shen; Horowitz, Eric D; Troupes, Andrew N et al. (2013) Engraftment of a galactose receptor footprint onto adeno-associated viral capsids improves transduction efficiency. J Biol Chem 288:28814-23
Gurda, Brittney L; DiMattia, Michael A; Miller, Edward B et al. (2013) Capsid antibodies to different adeno-associated virus serotypes bind common regions. J Virol 87:9111-24
Asokan, Aravind; Samulski, R Jude (2013) An emerging adeno-associated viral vector pipeline for cardiac gene therapy. Hum Gene Ther 24:906-13
Monahan, Paul E; Gui, Tong (2013) Gene therapy for hemophilia: advancing beyond the first clinical success. Curr Opin Hematol 20:410-6