Document 2283
 DOCN  M94A2283
 TI    GEM 91: therapeutic agent for AIDS based on antisense oligonucleotide
       approach.
 DT    9412
 AU    Agrawal S; Tang JY; Lisziewicz J; Gallo RC; Hybridon, Inc., Worcester,
       MA.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):34 (abstract no. 109A). Unique
       Identifier : AIDSLINE ICA10/94370292
 AB    Gene expression modulator 91 (GEM 91) is an oligonucleotide
       phosphorothioate (25-mer) designed to bind to the initiation site of gag
       gene. This site is found to be very conserved among various patient
       HIV-1 isolates and is critical for packaging of the virus. GEM 91 is
       rapidly taken up by various lymphocytes and is stable under
       physiological conditions. GEM 91 has been studied for its anti-HIV
       activity using laboratory as well as various primary isolates of HIV-1
       using MOLT-3, CEM, H9, PBMCs and macrophages. GEM 91 inhibited the virus
       replication in a sequence specific and dose dependent manner. GEM 91 is
       also found to be effective against AZT resistant primary HIV-1 isolates.
       Pharmacokinetic studies in mice, rats and monkeys have been performed
       and showed that GEM 91, if administered intravenously, is bioavailable
       in most of the organs, and half life of plasma clearance is in the range
       of 30-50 hours. In an acute toxicity study, GEM 91 has been administered
       to mice and rats at a dose of 500 mg/kg (intravenously) and up to a dose
       of 20 mg/kg (slow infusion), and found to be well tolerated. Presently,
       GEM 91 is in Phase I clinical trials at Agence Nationale de Recherches
       sur le SIDA (ANRS) in Paris. GEM 91 is also a clinical candidate at the
       AIDS Clinical Trial Group (ACTG) of NIAID, USA.
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY  Animal  Antiviral
       Agents/*THERAPEUTIC USE  Dose-Response Relationship, Drug  Half-Life
       Haplorhini  Mice  Oligonucleotides, Antisense/ADMINISTRATION & DOSAGE/
       PHARMACOKINETICS/*THERAPEUTIC USE  Rats  Thionucleotides/ADMINISTRATION
       & DOSAGE/PHARMACOKINETICS/  *THERAPEUTIC USE  Virus Replication/DRUG
       EFFECTS  CLINICAL TRIAL  CLINICAL TRIAL, PHASE I  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).