PMID: 9191019May 1, 1997Paper

Protection of hu-PBL-SCID/beige mice from HIV-1 infection by a 6-mer modified oligonucleotide, R-95288

Antiviral Research
T AgatsumaM Kaneko

Abstract

We analyzed the anti-HIV-1 activity of an oligonucleotide derivative, R-95288, in severe combined immunodeficient (SCID/beige) mice transplanted with normal human peripheral blood leukocytes (PBLs), designated hu-PBL-SCID/beige mice. The human chimeric mice were inoculated with HIV-1(CC1) 3 weeks after the transplantation and sacrificed 2 weeks later. Virus infection was determined by coculture of splenocytes with fresh human PBLs and also by detection of HIV- specific DNA sequences using the polymerase chain reaction. No evidence of infection was observed in mice treated with R-95288 (100 mg/kg/day) using intraperitoneal delivery by osmotic minipumps starting 1 day before virus challenge. In contrast, virus infection was observed in over 80% of the saline-treated control mice. In addition, partial inhibition of HIV-1 infection was obtained in mice treated subcutaneously with R-95288 (100 mg/kg/day). Toxicity towards the engrafted human cells was not observed by flow cytometric analysis. Moreover, R-95288 failed to inhibit lymphocyte proliferation (CC50 > 400 microg/ml), while 90% inhibition of HIV-1 replication was achieved at 3.1 microg/ml in vitro. These results suggest the ability of R-95288 to protect the human chimeric mi...Continue Reading

References

Dec 1, 1991·Immunological Reviews·B E TorbettD E Mosier
Feb 15, 1991·Science·D E MosierS A Spector
Nov 1, 1995·Nature Medicine·C A Stein
Jul 1, 1994·Immunology Today·D Mosier, H Sieburg

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Citations

Jun 14, 2003·Pharmacology & Therapeutics·Kathleen F PirolloEsther H Chang
Apr 9, 2001·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·T AbeH Takaku
Apr 30, 2003·Antiviral Chemistry & Chemotherapy·Paul F Torrence, Linda D Powell

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