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.
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.
|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|