John Libbey Eurotext



Gene therapy for the treatment of HIV infection Volume 3, issue 3, Mai - Juin 1999


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This review describes the main gene therapy strategies for the treatment of HIV infection. Intracellular immunization which protects transduced cells from infection encompasses several approaches such as the use of transdominant proteins, RNA decoys, antisens RNA or ribozymes. The selective destruction of infected cells by suicide genes, the use of inhibitory proteins like soluble CD4 represent other approaches. Genetic pharmacomodulation allows to improve the intracellular metabolism of drugs such as AZT by increasing its anti-reverse transcriptase activity. Genetic immunotherapy leads to an enhancement of the antiviral immune response by increasing the presentation of viral antigens to T lymphocytes after transfer of HIV genes into dendritic cells. In the second part of the review the practical aspects of gene therapy are discussed. This includes the choice of target cells such as hematopoietic stem cells, T lymphocytes or dendritic cells ; the choice of therapeutic vectors which depends both on the target cells and on the therapeutic strategies chosen. Finally, in view of developing clinical trials, one have to consider the notions of clinical efficiency and tolerance, the validation of the therapeutical strategies by using animal models, the preclinical steps that include scale up experiments performed under good manufacture and good laboratory procedure conditions and the writing of standard operating procedures.