Immune responses to gene therapy are important considerations in the development of effective vectors. In vivo delivery of recombinant adenoviruses have established important principles likely to be relevant to many other systems. Humoral immune responses develop to the capsid proteins of the input virus, which diminish the efficiency of vector readministration. Adenoviruses deleted of the E1 genes express viral proteins in the transduced cell, which activate destructive cytotoxic T lymphocytes (CTLs). Frequently, the transgene product can serve as a target for CTL, as well. Dr. Naren Chirmule was recruited to the Institute for Human Gene Therapy (IHGT) in 1996 to establish a core facility in immunology. This Core provides a large profile of an in vitro assays to measure cellular and humoral immune responses to vectors and transgene products. Included are analyses of CD4+ T cells (lymphoproliferation and cytokine release assays) as well as chromium release assays to assess CTLs. Humoral immune responses are measured through ELISA, Western Blots, isotype fractionation, and neutralizing assays. Viral and transgene products are evaluated as potential antigens in these assays. The Immunology Core provides full service to P30 investigators in areas of basic, translational, and clinical research. The core is a useful mechanism to assure standardization of assays across different protocols.

Project Start
1999-09-01
Project End
2000-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Svidritskiy, Egor; Korostelev, Andrei A (2018) Conformational Control of Translation Termination on the 70S Ribosome. Structure 26:821-828.e3
Svidritskiy, Egor; Korostelev, Andrei A (2018) Mechanism of Inhibition of Translation Termination by Blasticidin S. J Mol Biol 430:591-593
Gurda, Brittney L; De Guilhem De Lataillade, Adrien; Bell, Peter et al. (2016) Evaluation of AAV-mediated Gene Therapy for Central Nervous System Disease in Canine Mucopolysaccharidosis VII. Mol Ther 24:206-216
Svidritskiy, Egor; Madireddy, Rohini; Korostelev, Andrei A (2016) Structural Basis for Translation Termination on a Pseudouridylated Stop Codon. J Mol Biol 428:2228-36
Greig, Jenny A; Calcedo, Roberto; Grant, Rebecca L et al. (2016) Intramuscular administration of AAV overcomes pre-existing neutralizing antibodies in rhesus macaques. Vaccine 34:6323-6329
McClain, Lauren E; Davey, Marcus G; Zoltick, Phillip W et al. (2016) Vector serotype screening for use in ovine perinatal lung gene therapy. J Pediatr Surg 51:879-84
Calcedo, Roberto; Wilson, James M (2016) AAV Natural Infection Induces Broad Cross-Neutralizing Antibody Responses to Multiple AAV Serotypes in Chimpanzees. Hum Gene Ther Clin Dev 27:79-82
Svidritskiy, Egor; Korostelev, Andrei A (2015) Ribosome Structure Reveals Preservation of Active Sites in the Presence of a P-Site Wobble Mismatch. Structure 23:2155-61
Wang, Lili; Bell, Peter; Somanathan, Suryanarayan et al. (2015) Comparative Study of Liver Gene Transfer With AAV Vectors Based on Natural and Engineered AAV Capsids. Mol Ther 23:1877-87
Calcedo, Roberto; Franco, Judith; Qin, Qiuyue et al. (2015) Preexisting Neutralizing Antibodies to Adeno-Associated Virus Capsids in Large Animals Other Than Monkeys May Confound In Vivo Gene Therapy Studies. Hum Gene Ther Methods 26:103-5

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