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

Sánchez-Luque, Francisco J., Stich, Michael, Manrubia, Susanna, Briones, Carlos and Berzal-Herranz, Alfredo (2014). Efficient HIV-1 inhibition by a 16 nt-long RNA aptamer designed by combining in vitro selection and in silico optimisation strategies. Scientific Reports, 4 ,

Abstract

The 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.

Publication DOI: https://doi.org/10.1038/srep06242
Divisions: Engineering & Applied Sciences > Mathematics
Engineering & Applied Sciences > Systems analytics research institute (SARI)
Additional Information: This work is licensed under a Creative Commons Attribution-NonCommercial- NoDerivs 4.0 International License. The images or other third party material in thisarticle are included inthe article’s Creative Commonslicense, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http:// creativecommons.org/licenses/by-nc-nd/4.0/ Supplementary information: http://www.nature.com/scientificreports
Uncontrolled Keywords: Antivirals,small RNAs,RNA,General
Full Text Link: http://www.natu ... /srep06242.html
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2014-09-01
Authors: Sánchez-Luque, Francisco J.
Stich, Michael ( 0000-0001-8862-1044)
Manrubia, Susanna
Briones, Carlos
Berzal-Herranz, Alfredo

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