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Título

Efficient HIV-1 inhibition by a 16 nt-long RNA aptamer designed by combining in vitro selection and in silico optimisation strategies

AutorSánchez-Luque, Francisco J. CSIC ORCID; Stich, Michael CSIC ORCID; Manrubia Cuevas, Susanna CSIC ORCID ; Briones, Carlos CSIC ORCID; Berzal-Herranz, Alfredo CSIC ORCID
Palabras claveAntivirals
Small RNAs
RNA
Fecha de publicación1-sep-2014
EditorNature Publishing Group
CitaciónScientific Reports
ResumenThe human immunodeficiency virus type-1 (HIV-1) genome contains multiple, highly conserved structural RNA domains that play key roles in essential viral processes. Interference with the function of these RNA domains either by disrupting their structures or by blocking their interaction with viral or cellular factors may seriously compromise HIV-1 viability. RNA aptamers are amongst the most promising synthetic molecules able to interact with structural domains of viral genomes. However, aptamer shortening up to their minimal active domain is usually necessary for scaling up production, what requires very time-consuming, trial-and-error approaches. Here we report on the in vitro selection of 64 nt-long specific aptamers against the complete 5′-untranslated region of HIV-1 genome, which inhibit more than 75% of HIV-1 production in a human cell line. The analysis of the selected sequences and structures allowed for the identification of a highly conserved 16 nt-long stem-loop motif containing a common 8 nt-long apical loop. Based on this result, an in silico designed 16 nt-long RNA aptamer, termed RNApt16, was synthesized, with sequence 5′-CCCCGGCAAGGAGGGG-3′. The HIV-1 inhibition efficiency of such an aptamer was close to 85%, thus constituting the shortest RNA molecule so far described that efficiently interferes with HIV-1 replication.
Versión del editorhttp://dx.doi.org/10.1038/srep06242
URIhttp://hdl.handle.net/10261/113113
DOI10.1038/srep06242
E-ISSN2045-2322
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