Abstract

The goal of the studies dexcribed in this proposal is to develop gene transfer methods for the treatment of some human genetic diseases, with special reference to their application to the Lesch-Nyhan disease. We shall study the mechanisms of transfer of the HPRT gene and several other model genes by retroviral vectors into human and other mammalian cells in vitro and into whole mice by bone marrow repopulation and by systemic infection. Using optimally effecient retroviral vectors lacking all viral genes and other regulatory sequences thought to be harmful for recipient cells, we shall introduce the HPRT vector into patients with the Lesch-Nyhan disease, and determine if there is evidence in the patients of amelioration of the chemical or neurological aspects of the disorder.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020034-02
Application #
3317828
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1985-04-01
Project End
1990-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Chen, S T; Iida, A; Guo, L et al. (1996) Generation of packaging cell lines for pseudotyped retroviral vectors of the G protein of vesicular stomatitis virus by using a modified tetracycline inducible system. Proc Natl Acad Sci U S A 93:10057-62
Douar, A M; Themis, M; Sandig, V et al. (1996) Effect of amniotic fluid on cationic lipid mediated transfection and retroviral infection. Gene Ther 3:789-96
Iida, A; Chen, S T; Friedmann, T et al. (1996) Inducible gene expression by retrovirus-mediated transfer of a modified tetracycline-regulated system. J Virol 70:6054-9
Wang, M J; Friedmann, T; Johnson, P A (1995) Differentiation of PC12 cells by infection with an HSV-1 vector expressing nerve growth factor. Gene Ther 2:323-35
Miyanohara, A; Yee, J K; Bouic, K et al. (1995) Efficient in vivo transduction of the neonatal mouse liver with pseudotyped retroviral vectors. Gene Ther 2:138-42
Roemer, K; Johnson, P A; Friedmann, T (1995) Transduction of foreign regulatory sequences by a replication-defective herpes simplex virus type 1: the rat neuron-specific enolase promoter. Virus Res 35:81-9
Friedmann, T; Yee, J K (1995) Pseudotyped retroviral vectors for studies of human gene therapy. Nat Med 1:275-7
Lin, S; Gaiano, N; Culp, P et al. (1994) Integration and germ-line transmission of a pseudotyped retroviral vector in zebrafish. Science 265:666-9
Runnebaum, I B; Yee, J K; Kieback, D G et al. (1994) Wild-type p53 suppresses the malignant phenotype in breast cancer cells containing mutant p53 alleles. Anticancer Res 14:1137-44
Jinnah, H A; Wojcik, B E; Hunt, M et al. (1994) Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease. J Neurosci 14:1164-75

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