This project proposes to develop a novel approach to generate animal models of human disease. Current approaches to animal models are costly, difficult to maintain and largely limited to rodents all of which have significantly limited their utility for the development of useful human therapeutics. The proposed studies will take advantage of aptamer-based agents that we have previously made to transiently induce a factor IX deficient state in small and large animals and thus generate novel animal models for hemophilia B. If successful, these studies would pave the way for the generation of animal modes of many human diseases. Thus if funded the proposed studies could yield novel and potentially more useful animal models of human disease and in so doing pave the way for development of new therapeutic agents which can improve the health of the U.S. population.

Public Health Relevance

This Project proposes to develop a novel approach to generate animal models of human disease. Current animal models are costly and largely limited to rodents all of which significantly limited their utility forfhe development of human therapeutics. The proposed studies will take advantage of aptamer-based agents that we have previously made to transiently induce a factor IX deficient state in animals including primates that contain neutralizing AAV antibodies;

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
1P01HL112761-01A1
Application #
8460289
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
$398,440
Indirect Cost
$37,440
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

Showing the most recent 10 out of 34 publications