GENE-THERAPY AGAINST RETROVIRAL DISEASES

Eventually, gene therapy may be a valid option for chronic viral infec tions, including retroviral infections. Human retroviral diseases fit two categories: (1) those that result from a monoclonal outgrowth of a human T-cer( leukemia virus type I (HTLV-I)-infected cell, as in the case of adult T cell leukemia (ATL); and (2) those that appear to resu lt directly from virus load rather than monoclonal outgrowth - such as tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM) a nd human immunodeficiency virus (HIV)-associated acquired immune defic iency syndrome (AIDS). For ATL gene therapy, corrective mechanisms dir ected at regulatory sequences rather than viral sequences may be most important, though perhaps anti-tax therapy would be useful. For TSP/HA M and AIDS, gene therapy directed to control virus replication may be most useful. for anti-retroviral therapy, one may use dominant negativ e mutants and a variety of other approaches that direct toxins or comp ete out viral regulatory gene signal sequences. For maximum benefit, s uch therapy should be directed to different essential genes leg gag, p ol, env, fat or rev) involved in the virus replication cycle and utili ze different toxic approaches. A major impediment to the use of gene t herapy for AIDS is our inability to transfect a significant fraction o f target cells in vivo. Except for reconstituted mice, retroviral syst ems of animals have been underutilized as models for gene therapy. Nat urally occurring retroviral diseases of cats, goats, horses, and other species provide models for future development.