Technology evaluation: GEM-92, Hybridon Inc.
Hybridon is developing GEM-92, a second generation, orally administered antisense oligonucleotide directed against the gag gene in HIV-1 mRNA, as a potential treatment for HIV-1 infection and AIDS 11973841. It is a follow-up compound to GEM-91, which was discontinued due to dose-limiting toxicities [256660]. GEM-92 is undergoing phase I trials in the UK, in approximately 13 healthy volunteers. Hybridon intends to administer a single oral dose at one of three dose levels, while a fourth group will receive a single intravenous dose, in order to determine differences between oral and intravenous administration [263095]. GEM-92 has demonstrated significant inhibition of HIV-1 replication in various cell culture systems, and increased stability in comparison with GEM-91 [219621]. Hybridon has been issued two US patents; US-05652355 and US-05652356, claiming chemically advanced mixed backbone oligonucleotides [257135].
Zheng
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Department of Immunology, St Bartholomew's Hospital, London, UK. r.q.zheng@mds.qmw.ac.uk
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D004353:Drug Evaluation, Preclinical; D015750:Genes, gag; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000882:Haplorhini; D006801:Humans; D051379:Mice; D009838:Oligodeoxyribonucleotides; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D010330:Patents as Topic; D051381:Rats; D013329:Structure-Activity Relationship; D013873:Thionucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; C442420:GEM 92; D009838:Oligodeoxyribonucleotides; D020319:Oligodeoxyribonucleotides, Antisense; D013873:Thionucleotides; C079996:GEM91