The treatment of disease by genetic manipulation is emerging as a practical tool in medicine. The goal of this program project is to contribute to the development of gene therapy as a therapeutic modality through the study of model systems. The focus of the project is to use model systems to reveal obstacles and provide solutions to the impediments to gene therapy. Cellular and animal models will be employed to study transfer of potentially therapeutic genes, promote their expression, and measure the effects on a system that is predictive of similar responses in man. While clinical trials are not foreseen as within the scope of the proposal for all four projects the studies proposed in the program are intended to provide substantial information upon which clinical trials will be based. The program seeks through its four interactive projects and four cores to contribute data relevant to the general approach of gene therapy. While diverse in the organ systems studied in the program, the central purpose of the project is single and focused on the methods of gene transfer that may be needed to target and express human genes in different tissues. This goal will be accomplished by a thorough analysis of the vectors developed to transfer a variety of genes and by consideration of the problems of transduction and expression that are peculiar to each model system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
1P01DK044935-01A1
Application #
3095708
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1993-06-01
Project End
1998-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Han, Fang; Miyagawa, Yoshitaka; Verlengia, Gianluca et al. (2018) Cellular Antisilencing Elements Support Transgene Expression from Herpes Simplex Virus Vectors in the Absence of Immediate Early Gene Expression. J Virol 92:
Verlengia, Gianluca; Miyagawa, Yoshitaka; Ingusci, Selene et al. (2017) Engineered HSV vector achieves safe long-term transgene expression in the central nervous system. Sci Rep 7:1507
Miyagawa, Yoshitaka; Verlengia, Gianluca; Reinhart, Bonnie et al. (2017) Deletion of the Virion Host Shut-off Gene Enhances Neuronal-Selective Transgene Expression from an HSV Vector Lacking Functional IE Genes. Mol Ther Methods Clin Dev 6:79-90
Laemmle, Lillian L; Cohen, Justus B; Glorioso, Joseph C (2016) Constitutive Expression of GATA4 Dramatically Increases the Cardiogenic Potential of D3 Mouse Embryonic Stem Cells. Open Biotechnol J 10:248-257
Goins, William F; Hall, Bonnie; Cohen, Justus B et al. (2016) Retargeting of herpes simplex virus (HSV) vectors. Curr Opin Virol 21:93-101
Reinhart, Bonnie; Goins, William F; Harel, Asaff et al. (2016) An HSV-based library screen identifies PP1? as a negative TRPV1 regulator with analgesic activity in models of pain. Mol Ther Methods Clin Dev 3:16040
Miyagawa, Yoshitaka; Marino, Pietro; Verlengia, Gianluca et al. (2015) Herpes simplex viral-vector design for efficient transduction of nonneuronal cells without cytotoxicity. Proc Natl Acad Sci U S A 112:E1632-41
Majima, Tsuyoshi; Funahashi, Yasuhito; Takai, Shun et al. (2015) Herpes Simplex Virus Vector-Mediated Gene Delivery of Poreless TRPV1 Channels Reduces Bladder Overactivity and Nociception in Rats. Hum Gene Ther 26:734-42
Sha, Huizi; Zou, Zhengyun; Xin, Kai et al. (2015) Tumor-penetrating peptide fused EGFR single-domain antibody enhances cancer drug penetration into 3D multicellular spheroids and facilitates effective gastric cancer therapy. J Control Release 200:188-200
Goins, William F; Huang, Shaohua; Cohen, Justus B et al. (2014) Engineering HSV-1 vectors for gene therapy. Methods Mol Biol 1144:63-79

Showing the most recent 10 out of 210 publications