Glucose conjugation of anti-HIV-1 oligonucleotides containing unmethylated CpG motifs reduces their immunostimulatory activity.
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.
['Reyes-Darias|José A|JA|', 'Sánchez-Luque|Francisco J|FJ|', 'Morales|Juan Carlos|JC|', 'Pérez-Rentero|Sonia|S|', 'Eritja|Ramón|R|', 'Berzal-Herranz|Alfredo|A|']
D000276:Adjuvants, Immunologic D019380:Anti-HIV Agents D001483:Base Sequence D018899:CpG Islands D005947:Glucose D015658:HIV Infections D015497:HIV-1 D006801:Humans D019169:Jurkat Cells D016376:Oligonucleotides, Antisense D013873:Thionucleotides
oligonucleotides HIV-1 inhibition antiviral agents glycoconjugates immune response reduction