Restriction endonucleases are bacterial enzymes which protect bacteria against viral infections by cleaving the viral DNA at specific sites. Experiments have been performed to assess whether the activity of such enzymes can mediate anti-viral effects in mammalian models of virus infection. Results indicate that SV-40 infection can be modified by treatment with restriction endonucleases which cleave the SV-40 genome at the predicted site but not by restriction endonucleases which lack a cleavage site on the viral DNA. Studies are in progress which assess whether retrovirus infection, in which the RNA viral genome undergoes reverse transcription to dsDNA, is potentially susceptible to restriction endonucleases. Results to date indicate that restriction endonucleases which possess a target site on the HIV reverse transcribed DNA genome inhibit infection in vitro whereas restriction endonucleases which lack a specific recognition site have no effect on the course of infection. Studies in which the specificity of the effect is more precisely examined are underway. In vivo studies were undertaken to assess the activity of restriction endonucleases in vivo in a mouse retroviral model (MAIDS). Restriction endonucleases were loaded into liposomes as an effective delivery system and injected into LP-BM5 infected mice as well as controls. Preliminary studies revealed that a) there were no toxic effects of the restriction endonuclease-liposomes in the healthy control mice and b) there was modest suppression of disease in the infected animals. Furthermore, the endonuclease-liposome construct was shown to be very stable in that 31/2 months following construction, restriction endonucleases retained their specific cutting activity. Future experiments will expand the scope of these studies.
