AEGiS-11IAC: Ribozyme-based gene therapy approach for the treatment of HIV-1 infection.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

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Ribozyme-based gene therapy approach for the treatment of HIV-1 infection.

Int Conf AIDS 1996 Jul 7-12; 11:10 (abstract no. We.A.273)
Sun LQ, Gerlach W, Symonds G; RW Johnson Pharmaceutical Research Institute, Sydney, Australia. Fax: 61-2-360 9812. E-mail: sun@angis.su.oz.au.

OBJECTIVE: To develop an ribozyme-based gene therapy strategy for inhibition of HIV-1 replication in human hemopoietic lymphocytes.

METHODS: Hammerhead ribozymes targeted to the HIV-1 y packaging site and regions of the tat gene were designed and synthesised. The ribozymes were engineered into expression constructs and transfected into T cells lines. The anti-y and anti-tat site ribozymes were also separately cloned into MoML V-based retroviral vectors. These were packaged in a two step procedure and amphotropic retroviruses were used to transduce both T lymphocytic cell lines and primary CD4+ enriched peripheral blood lymphocytes (PBLs) for validation of those therapeutic retroviruses.

RESULTS: Ribozyme sequences were constitutively expressed in both T cell lines (for over 6 months) and PBLs, and no apparent cellular cytotoxicity was observed in the transduced cells. When tested, HIV-1 replication was found to be markedly inhibited in T cell lines (both pooled and clonal) and PBLs challenged with either laboratory HIV-1 strains such as IIIB, or primary clinical isolates. Clinical trials based on the anti-tat ribozymes are planned based on a CD4+ and a CD34+ strategy to address questions of safety, potential toxicity and longevity of transduced cell survival.

CONCLUSIONS: An anti-tat ribozyme has been shown effective in inhibition of HIV-1 replication in several assay systems. This ribozyme construct has reached the human clinical trial stage for evaluation as an anti-HIV agent.

Keywords: AEGIS, HIV Infections, RNA, Catalytic, Gene Therapy, HIV-1, Genes, tat, Virus Replication, Genetic Vectors, Retroviridae, Cell Line, T-Lymphocytes, RNA, Antisense, Lymphocytes, hammerhead ribozyme, Human, therapy, genetics, virology, drug therapy, ICA11

960707
WeA273

Copyright © 1996 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.