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 for the 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 #
5P01HL112761-02
Application #
8616794
Study Section
Heart, Lung, and Blood Program Project Review Committee (HLBP)
Project Start
Project End
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
City
Chapel Hill
State
NC
Country
United States
Zip Code
Chai, Zheng; Samulski, R Jude; Li, Chengwen (2018) Nab Escaping AAV Mutants Isolated from Mouse Muscles. Bio Protoc 8:
Sun, Junjiang; Shao, Wenwei; Chen, Xiaojing et al. (2018) An Observational Study from Long-Term AAV Re-administration in Two Hemophilia Dogs. Mol Ther Methods Clin Dev 10:257-267
Chai, Zheng; Zhang, Xintao; Rigsbee, Kelly Michelle et al. (2018) Cryoprecipitate augments the global transduction of the adeno-associated virus serotype 9 after a systemic administration. J Control Release 286:415-424
Tse, Longping V; Moller-Tank, Sven; Meganck, Rita M et al. (2018) Mapping and Engineering Functional Domains of the Assembly-Activating Protein of Adeno-associated Viruses. J Virol 92:
Albright, Blake H; Storey, Claire M; Murlidharan, Giridhar et al. (2018) Mapping the Structural Determinants Required for AAVrh.10 Transport across the Blood-Brain Barrier. Mol Ther 26:510-523
Berry, Garrett E; Tse, Longping V (2017) Virus Binding and Internalization Assay for Adeno-associated Virus. Bio Protoc 7:
Tse, Longping Victor; Klinc, Kelli A; Madigan, Victoria J et al. (2017) Structure-guided evolution of antigenically distinct adeno-associated virus variants for immune evasion. Proc Natl Acad Sci U S A 114:E4812-E4821
Liang, Katharine J; Woodard, Kenton T; Weaver, Mark A et al. (2017) AAV-Nrf2 Promotes Protection and Recovery in Animal Models of Oxidative Stress. Mol Ther 25:765-779
Wang, M; Sun, J; Crosby, A et al. (2017) Direct interaction of human serum proteins with AAV virions to enhance AAV transduction: immediate impact on clinical applications. Gene Ther 24:49-59
Chai, Zheng; Sun, Junjiang; Rigsbee, Kelly Michelle et al. (2017) Application of polyploid adeno-associated virus vectors for transduction enhancement and neutralizing antibody evasion. J Control Release 262:348-356

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