Matsukura M, Suzuki T, Shimada T; International Conference on AIDS.
Int Conf AIDS. 1996 Jul 7-12; 11: 62 (abstract no. Mo.A.1043).
Dept. of Child Devel., Kumamoto Univ. School of Medicine, Kumamoto City, Japan. Fax: 96-373-5200.
Objective: To examine the feasibility of the use of HIV vectors in AIDS gene therapy. Methods: The herpes simplex virus thymidine kinase (HSV-TK) suicide gene was inserted between the packaging signal and the neo gene of pHXN, yielding pHXTKN. The HSVTK gene is directed by the HIV-LTR, while the neo gene is by the internal tk promoter. Other HIV vector plasmids are splicing mutant(pHXCmTKN), CMV promoter+TK (pHXCTKN) and its reversed (pHXNCTK). Results: CD4+HeLa cells and H9 cells were tranduced with the vectors and were selected with G418. The bulk cultures carrying HXTKN were found to be highly sensitive to GCV one to two weeks after de novo infection of HIVIIIb. The therapeutic index (ratio of GCV IC50 between HIV uninfected cells and infected cells) was approximately two degree of magnitude in MTT assay, suggesting that HIV infection efficiently induced expression of the HSVTK gene. While other cultures carrying HXN, HXCmTKN or HXNCTK are not sensitive to GCV, bulk culture carrying HXCTKN was profoundly sensitive to GCV even without HIV infection. Conclusions: T cell specific gene transfer, HIV specific gene expression and in vitro and in vivo selection of HIV uninfected cells using the HIV vector may provide a novel strategy of gene therapy for AIDS.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Antiretroviral Therapy, Highly Active
- Gene Therapy
- Genetic Vectors
- HIV Infections
- HIV Seropositivity
- Hela Cells
- Humans
- In Vitro
- Plasmids
- Thymidine Kinase
- genetics
Other ID:
UI: 102217013
From Meeting Abstracts