PROTECTION OF HU-PBL-SCID BEIGE MICE FROM HIV-1 INFECTION BY A 6-MER MODIFIED OLIGONUCLEOTIDE, R-95288/

We analyzed the anti-HIV-1 activity of an oligonucleotide derivative, R-95288, in severe combined immunodeficient (SCID/beige) mice transpla nted with normal human peripheral blood leukocytes (PBLs), designated hu-PBL-SCID/beige mice, The human chimeric mice were inoculated with H IV-1(CC1) 3 weeks after the transplantation and sacrificed 2 weeks lat er. Virus infection was determined by coculture of splenocytes with fr esh human PBLs and also by detection of HIV- specific DNA sequences us ing the polymerase chain reaction. No evidence of infection was observ ed in mice treated with R-95288 (100 mg/kg/day) using intraperitoneal delivery by osmotic minipumps starting 1 day before virus challenge. I n contrast, virus infection was observed in over 80% of the saline-tre ated control mice. In addition, partial inhibition of HIV-1 infection was obtained in mice treated subcutaneously with R-95288 (100 mg/kg/da y). Toxicity towards the engrafted human cells was not observed by flo w cytometric analysis. Moreover, R-95288 failed to inhibit lymphocyte proliferation (CC50 > 400 mu g/ml), while 90% inhibition of HIV-1 repl ication was achieved at 3.1 mu g/ml in vitro. These results suggest th e ability of R-95288 to protect the human chimeric mice against HIV-1 infection. (C) 1997 Elsevier Science B.V.