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Glucose conjugation of anti-HIV-1 oligonucleotides containing unmethylated CpG motifs reduces their immunostimulatory activity

AuthorsReyes-Darias, José Antonio; Sánchez-Luque, Francisco J.; Morales, Juan C.; Pérez-Rentero, Sonia; Eritja Casadellà, Ramón ; Berzal-Herranz, Alfredo
KeywordsGlucose DNA oligonucleotides
HIV-1 inhibition
Immune response reduction
Conjugated oligonucleotides
Issue Date2015
PublisherJohn Wiley & Sons
CitationChembiochem : a European journal of chemical biology 16: 584- 591 (2015)
Abstract© 2015 Wiley-VCH Verlag GmbH & Co. KGaA. 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.
Identifiersdoi: 10.1002/cbic.201402574
issn: 1439-7633
Appears in Collections:(IIQ) Artículos
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