PROGRESS TOWARDS GENE-THERAPY FOR HIV-INFECTION

The retroviral life cycle and genetic plasticity of human immunodefici ency virus 1 (HIV-1) present unprecedented therapeutic challenges. Twe lve years into the HIV epidemic, satisfactory treatment remains elusiv e. Our current understanding of AIDS pathogenesis calls for early inte rvention with antiviral agents. Although still in its infancy, human g ene therapy holds considerable potential for the long term treatment o f genetic disorders, cancer and chronic infectious diseases. Gene ther apy for HIV infection is receiving particularly intensive study: appro aches that are in development include both immunotherapy (e.g. therape utic vaccines and adoptive transfer of CD8(+) T-cell clones) and direc t antiviral therapy (intracellular immunization). The latter strategie s include transdominant modifications of HIV proteins, RNA decoys, ant isense RNA, ribozymes and modifications of cellular proteins (e.g. int racellular antibodies, soluble CD4). Several of these strategies are n ow entering clinical trials. While significant conceptual and technica l hurdles remain to be overcome before the promise of gene therapy for HIV infection can be fully realized, progress in this field is likely to be rapid and to contribute to the border applicability of human ge ne therapy to the treatment of other disorders.