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Título: | Glucose conjugation of anti-HIV-1 oligonucleotides containing unmethylated CpG motifs reduces their immunostimulatory activity |
Autor: | Reyes-Darias, José Antonio CSIC ORCID; Sánchez-Luque, Francisco J. CSIC ORCID; Morales, Juan C.; Pérez-Rentero, Sonia CSIC ORCID; Eritja Casadellà, Ramón CSIC ORCID ; Berzal-Herranz, Alfredo CSIC ORCID | Palabras clave: | Glucose DNA oligonucleotides HIV-1 inhibition Immune response reduction Conjugated oligonucleotides |
Fecha de publicación: | 2015 | Editor: | John Wiley & Sons | Citación: | Chembiochem : a European journal of chemical biology 16: 584- 591 (2015) | Resumen: | © 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. | URI: | http://hdl.handle.net/10261/113463 | DOI: | 10.1002/cbic.201402574 | Identificadores: | doi: 10.1002/cbic.201402574 issn: 1439-7633 |
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