Abstract

The Human Applications Laboratory (HAL) of the Institute of Human Gene Therapy (IHGT) was established in 1993 to provide manufacturing capability for pilot human experiments. This facility provided clinical grade retrovirus for an ex vivo trial of gene therapy in familial hypercholesterolemia. More recently HAL has focused on recombinant adenoviruses providing support to six clinical trials including those involving cystic fibrosis and ornithine transcarbamylase. The concept of HAL has evolved to incorporate production, quality control and development of improved methods for manufacturing. The pilot manufacturing facility recently underwent substantial renovations and restructuring to allow the concurrent production of different classes of vectors. An important priority is the development of manufacturing and purification methods for adeno-associated virus (AAV). Clinical grade production of AAV should come on-line later this spring with planned applications to a number of genetic diseases such as hemophilia, retinitis pigmentosa, lysosomal storage diseases, and inherited myopathies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK047757-07
Application #
6201907
Study Section
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

  Institution

Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

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

Showing the most recent 10 out of 231 publications