Problems and Prospects of Gene Therapy Against HIV

Abstract

Possibilities for the application of gene therapy based on insertion of transgenes into a patient’s cells in order to express anti-HIV agents interfering with the virus life cycle analogously to highly active antiretroviral therapy (HAART) were reviewed. Anti-HIV agents based on various types of RNA (ribozymes, antisense RNA, RNA aptamers, RNA decoys, small interfering RNA) and protein agents such as RevM10, intracellular antibodies, and intrakines were described. Results of the first clinical trials showed that one of the principal problems of gene therapy is the maintenance in modified cells of the required level of anti-HIV activity. Several gene-therapy strategies for suppressing expression of chemokine co-receptor CCR5 are known; however, the activity of agents integrated in the anti-CCR5 genome decayed over time (gene silencing). Special attention was paid to the development of a treatment method for HIV-infected cells that used tre-recombinases. Preliminary experiments showed that the use of these drugs led to excision of the integrated HIV proviral DNAfrom the genome in cell lines and mice. This was a promising way to destroy latent virus reservoirs and eradicate the virus from the body. It was concluded that gene therapy will become the most important theme of long-term scientific pharmaceutical developments because it could potentially provide effective treatment or even complete cure of HIV-infection after a single administration.