AEGiS-10IAC: Gene therapy for HIV infection.

10th International AIDS Conference


Yokohama, Japan — Aug 7-12, 1994

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Gene therapy for HIV infection.

Int Conf AIDS 1994 Aug 7-12; 10:4 (abstract no. PS18)
Wong-Staal F, Yu M, Yamada O, Leavitt M, Maruyama A; UCSD, La Jolla.

OBJECTIVE: The goal of gene therapy for HIV infection is to repopulate the immune system with genetically altered cells that resist infection. Our group has been developing a hairpin ribozyme that cleaves HIV-1 RNA as a form of gene therapy, and have demonstrated in vivo efficacy in both lymphocytes and monocytes derived from progenitor cells.

METHODS: Peripheral blood lymphocytes were enriched for CD4 cells. Transduced cells were selected with G418 and challenged with HIV-1. Transduction of precursor cells was carried out with immunoaffinity enriched, prestimulated CD34 cells. Differentiation into monocytes occurred in the presence of GM-CSF.

RESULTS: Primary T-cells transduced with retroviral vectors containing the ribozyme were resistant to challenge with diverse strains of HIV, including clinical isolates. Hematopoietic stem/progenitor cells from adult bone marrow, fetal cord blood or mobilized peripheral blood transduced by the vector expressed the ribozyme efficiently and persistently in the CFUs. Transduction and ribozyme expression had no apparent deleterious effect on cell phenotypes or proliferation. The cultured stem cells differentiated into macrophages/monocytes and those derived from the ribozyme transduced stem cells withstood HIV infection in vitro.

DISCUSSION AND CONCLUSIONS: Ribozyme gene therapy may be an effective preemptive strategy for interfering with HIV replication. A phase I clinical protocal to test the safety and function of the ribozyme in transduced human PBL in vivo has been developed and approved by the NIH RAC.

Keywords: AEGIS, HIV Infections, Gene Therapy, HIV-1, Antigens, CD34, RNA, Catalytic, Genetic Vectors, Virus Replication, Monocytes, Macrophages, Lymphocytes, T-Lymphocytes, hairpin ribozyme, Adult, Human, In Vitro, virology, ICA10KWDaegis,hivinfections,genetherapy,hiv-1,antigens,cd34,rna,catalytic,geneticvectors,virusreplication,monocytes,macrophages,lymphocytes,t-lymphocytes,hairpinribozyme,adult,human,invitro,virology,ica10
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PS18

Copyright © 1994 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.