gem91 and HIV-Infections

gem91 has been researched along with HIV-Infections* in 11 studies

Reviews

1 review(s) available for gem91 and HIV-Infections

ArticleYear
Targeting the HIV-1 RNA leader sequence with synthetic oligonucleotides and siRNA: chemistry and cell delivery.
    Biochimica et biophysica acta, 2006, Volume: 1758, Issue:3

    New candidates for development as potential drugs or virucides against HIV-1 infection and AIDS continue to be needed. The HIV-1 RNA leader sequence has many essential functional sites for virus replication and regulation that includes several highly conserved sequences. The review describes the historical context of targeting the HIV-1 RNA leader sequence with antisense phosphorothioate oligonucleotides, such as GEM 91, and goes on to describe modern approaches to targeting this region with steric blocking oligonucleotide analogues having newer and more advantageous chemistries, as well as recent studies on siRNA, towards the attainment of antiviral activity. Recent attempts to obtain improved cell delivery are highlighted, including exciting new developments in the use of peptide conjugates of peptide nucleic acid (PNA) as potential virucides.

    Topics: 5' Untranslated Regions; Anti-HIV Agents; HIV Infections; HIV-1; Humans; Oligodeoxyribonucleotides, Antisense; RNA, Small Interfering; RNA, Viral; Thionucleotides

2006

Trials

1 trial(s) available for gem91 and HIV-Infections

ArticleYear
Pharmacokinetics of an anti-human immunodeficiency virus antisense oligodeoxynucleotide phosphorothioate (GEM 91) in HIV-infected subjects.
    Clinical pharmacology and therapeutics, 1995, Volume: 58, Issue:1

    Human pharmacokinetics of an antisense oligodeoxynucleotide phosphorothioate (GEM 91) developed as an anti-human immunodeficiency virus (HIV) agent was carried out in this study. 35S-Labeled GEM 91 was administered to six HIV-infected individuals by means of 2-hour intravenous infusions at a dose of 0.1 mg/kg. Plasma disappearance curves for GEM 91-derived radioactivity could be described by the sum of two exponentials, with half-life values of 0.18 +/- 0.04 and 26.71 +/- 1.67 hours. The radioactivity in plasma was further evaluated by polyacrylamide gel electrophoresis, showing the presence of both intact GEM 91 and lower molecular weight metabolites. Urinary excretion represented the major pathway of elimination, with 49.15% +/- 6.80% of the administered dose excreted within 24 hours and 70.37% +/- 6.72% over 96 hours after dosing. The radioactivity in urine was associated with lower molecular weight metabolites. No drug-related toxicity was observed.

    Topics: Adult; Antiviral Agents; Base Sequence; Chromatography, High Pressure Liquid; Electrophoresis, Polyacrylamide Gel; HIV Infections; Humans; Infusions, Intravenous; Male; Molecular Sequence Data; Oligodeoxyribonucleotides, Antisense; Oligonucleotides, Antisense; Sulfur Radioisotopes; Thionucleotides; Tissue Distribution

1995

Other Studies

9 other study(ies) available for gem91 and HIV-Infections

ArticleYear
Glucose conjugation of anti-HIV-1 oligonucleotides containing unmethylated CpG motifs reduces their immunostimulatory activity.
    Chembiochem : a European journal of chemical biology, 2015, Mar-02, Volume: 16, Issue:4

    Antisense oligodeoxynucleotides (ODNs) are short synthetic DNA polymers complementary to a target RNA sequence. They are commonly designed to halt a biological event, such as translation or splicing. ODNs are potentially useful therapeutic agents for the treatment of different human diseases. Carbohydrate-ODN conjugates have been reported to improve the cell-specific delivery of ODNs through receptor mediated endocytosis. We tested the anti-HIV activity and biochemical properties of the 5'-end glucose-conjugated GEM 91 ODN targeting the initiation codon of the gag gene of HIV-1 RNA in cell-based assays. The conjugation of a glucose residue significantly reduces the immunostimulatory effect without diminishing its potent anti-HIV-1 activity. No significant effects were observed in either ODN stability in serum, in vitro degradation of antisense DNA-RNA hybrids by RNase H, cell toxicity, cellular uptake and ability to interfere with genomic HIV-1 dimerisation.

    Topics: Adjuvants, Immunologic; Anti-HIV Agents; Base Sequence; CpG Islands; Glucose; HIV Infections; HIV-1; Humans; Jurkat Cells; Oligonucleotides, Antisense; Thionucleotides

2015
Highly organized self-assembled dendriplexes based on poly(propylene imine) glycodendrimer and anti-HIV oligodeoxynucleotides.
    Current medicinal chemistry, 2012, Volume: 19, Issue:27

    Dendrimers are artificial polymeric macromolecules which are widely considered to be a promising tool for future gene therapy applications. They have been used as efficient delivery vehicles for antisense oligonucleotides targeting the interior of cells. We demonstrate that dendriplexes formed from anti-HIV oligodeoxynucleotides ANTI-TAR, GEM91, and SREV in complex with generation 4 maltose (PPI-Mal G4) and maltotriose (PPI-Mal-III G4) modified poly(propylene imine) dendrimers are able to self-assemble into highly organized 1D and 3D nanostructures. The resulting nanostructures were characterized by fluorescence methods, laser Doppler electrophoresis, dynamic light scattering (DLS), atomic force microscopy (AFM) and molecular modeling. The results show that ANTI-TAR and GEM 91 dendriplexes self-assemble into fibrils with length scales up to several hundreds of nm. SREV, on the contrary, forms quadrilateral- like 3D nanostructures. A good correlation between the various experimental methods and molecular modeling indicates the formation of those nanostructures in solution. Space symmetry of the oligonucleotides and the resulting dendriplex monomeric units are probably the most important factors which influence the way of self-assembling.

    Topics: Anti-HIV Agents; Dendrimers; Fluorescence Polarization; HIV Infections; Humans; Light; Maltose; Models, Molecular; Nanostructures; Oligonucleotides, Antisense; Polypropylenes; Scattering, Radiation; Thionucleotides

2012
Technology evaluation: GEM-92, Hybridon Inc.
    Current opinion in molecular therapeutics, 1999, Volume: 1, Issue:4

    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].

    Topics: Animals; Anti-HIV Agents; Clinical Trials, Phase I as Topic; Drug Evaluation, Preclinical; Genes, gag; Haplorhini; HIV Infections; HIV-1; Humans; Mice; Oligodeoxyribonucleotides; Oligodeoxyribonucleotides, Antisense; Patents as Topic; Rats; Structure-Activity Relationship; Thionucleotides; Virus Replication

1999
The multiple inhibitory mechanisms of GEM 91, a gag antisense phosphorothioate oligonucleotide, for human immunodeficiency virus type 1.
    AIDS research and human retroviruses, 1997, May-01, Volume: 13, Issue:7

    GEM 91 (gene expression modulator) is a 25-mer oligonucleotide phosphorothioate complementary to the gag initiation site of HIV-1. GEM 91 has been studied in various in vitro cell culture models to examine inhibitory effects on different stages of HIV-1 replication. Experiments were focused on the binding of virions to the cell surface, inhibition of virus entry, reverse transcription (HIV DNA production), inhibition of steady state viral mRNA levels, inhibition of virus production from chronically infected cells, and inhibition of HIV genome packaging within virions. Experiments were also performed in vitro in an attempt to generate strains of HIV with reduced sensitivity to GEM 91. We observed sequence-dependent inhibition of virus entry/reverse transcription and a reduction in steady state viral RNA levels. We also observed sequence-independent inhibition of virion binding to cells and inhibition of virus production by chronically infected cells. Using in vitro methods that were successful in generating HIV strains with reduced sensitivity to AZT, we were unable to generate strains with reduced sensitivity to GEM 91.

    Topics: Anti-HIV Agents; Blotting, Northern; Cells, Cultured; DNA Replication; Drug Resistance, Microbial; HIV Infections; HIV-1; Humans; Oligodeoxyribonucleotides, Antisense; Oligonucleotides, Antisense; RNA, Messenger; RNA, Viral; Thionucleotides; Transcription, Genetic; Virus Assembly; Virus Replication; Zidovudine

1997
In vivo metabolic profile of a phosphorothioate oligodeoxyribonucleotide.
    Antisense & nucleic acid drug development, 1997, Volume: 7, Issue:3

    Antisense phosphorothioate oligodeoxyribonucleotides (PS oligonucleotides) have the ability to inhibit individual gene expression in the potential treatment of cancer and viral diseases. Following administration in vivo, PS oligonucleotides are rapidly cleared from the plasma and distributed to various organs. However, the manner in which administered oligonucleotides are metabolized in plasma and tissues is poorly understood. In this study, a 25-mer PS oligonucleotide (GEM91) complementary to the gag gene mRNA of the human immunodeficiency virus (HIV-1) was administered to mice through intravenous injections to investigate its metabolism. The PS oligonucleotide was extracted from plasma at 1 hour postadministration and from kidney and liver at 24 hours postadministration. After extraction, the PS oligonucleotide and its metabolites were tailed with dA and annealed to a dT-tailed plasmid. The recombinant plasmid was ligated and used to transform competent bacteria. The region of interest containing the PS oligonucleotide was then sequenced. Our results show that degradation of the PS oligonucleotide in plasma was primarily from the 3'-end. However, in kidney and liver, degradation was primarily from the 3'-end, but a large proportion of the PS oligonucleotide was degraded from the 5'-end as well. We also studied the metabolism of PS oligonucleotide in plasma after 2-hour intravenous infusion in HIV-infected patients. The degradation of the PS oligonucleotide in plasma was primarily from the 3'-end. This study is important in understanding the metabolism of antisense PS oligonucleotide in vivo in general but also provides guidance for designing second-generation antisense oligonucleotides with improved stability and safety profile.

    Topics: Animals; Anti-HIV Agents; Biotransformation; DNA, Recombinant; Genes, gag; HIV Infections; HIV-1; Humans; Infusions, Intravenous; Kidney; Liver; Male; Mice; Oligodeoxyribonucleotides, Antisense; Oligonucleotides, Antisense; RNA, Messenger; RNA, Viral; Sequence Analysis, DNA; Thionucleotides; Tissue Distribution; Transformation, Bacterial

1997
Clinical trial results of GEM91 show activity against advance HIV.
    AIDS patient care and STDs, 1997, Volume: 11, Issue:4

    Topics: Anti-HIV Agents; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; HIV Infections; HIV-1; Humans; Oligodeoxyribonucleotides, Antisense; Oligonucleotides, Antisense; RNA, Viral; Thionucleotides

1997
Significant inhibitory effects of Hybridon's antisense compound on various HIV-1 replication steps in in vitro tests.
    AIDS patient care and STDs, 1996, Volume: 10, Issue:6

    Topics: Antiviral Agents; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Resistance, Microbial; HIV Infections; HIV-1; Humans; Oligodeoxyribonucleotides, Antisense; Oligonucleotides, Antisense; Thionucleotides; Virus Replication

1996
Still looking for the real GEM.
    GMHC treatment issues : the Gay Men's Health Crisis newsletter of experimental AIDS therapies, 1996, Volume: 10, Issue:4

    Excitement caused by reports of the GEM 91, the first antisense drug to be used against HIV, has been dampened by results of clinical trials. GEM 91 is broken down in the body too quickly for it to reach effective concentrations. New formulations are being developed that will hopefully work better. A phase I AZT/GEM 91 interaction trial using a new formulation is planned.

    Topics: Antiviral Agents; Genes, Viral; HIV Infections; HIV-1; Oligodeoxyribonucleotides, Antisense; Oligonucleotides, Antisense; Thionucleotides; Virus Replication

1996
Sense antisense nonantisense. Can these novel antivirals knock HIV senseless?
    Journal of the International Association of Physicians in AIDS Care, 1995, Volume: 1, Issue:1

    The authors examine the development, theories, research, and use of antivirals in the response to HIV infection and AIDS progression and address the question of how effective this novel approach may be. The article includes discussions that detail the antisense and triple helix candidates for HIV and related conditions, the hurdles that exist in the development of antisense oligonucleotides, and the way triple helix and antisense oligonucleotides disrupt a genetic message.

    Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; Binding Sites; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cytomegalovirus Retinitis; DNA, Viral; HIV; HIV Infections; Humans; Nucleic Acid Conformation; Oligodeoxyribonucleotides, Antisense; Oligonucleotides, Antisense; RNA, Viral; Thionucleotides

1995