Inhibition of HIV-1 replication and dimerization interference by dual inhibitory RNAs.

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Francisco J Sánchez-LuqueA Berzal-Herranz

Abstract

The 5'-untranslated region (5'UTR) of the HIV-1 RNA is an attractive target for engineered ribozymes due to its high sequence and structural conservation. This region encodes several conserved structural RNA domains essential in key processes of the viral replication and infection cycles. This paper reports the inhibitory effects of catalytic antisense RNAs composed of two inhibitory RNA domains: an engineered ribozyme targeting the 5' UTR and a decoy or antisense domain of the dimerization initiation site (DIS). These chimeric molecules are able to cleave the HIV-1 5'UTR efficiently and prevent viral genome dimerization in vitro. Furthermore, catalytic antisense RNAs inhibited viral production up to 90% measured as p24 antigen levels in ex vivo assays. The use of chimeric RNA molecules targeting different domains represents an attractive antiviral strategy to be explored for the prevention of side effects from current drugs and of the rapid emergence of escape variants of HIV-1.

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Citations

Jul 30, 2014·Molecular Therapy. Nucleic Acids·Robert J ScarboroughAnne Gatignol
Apr 17, 2014·FEBS Letters·Sumona Karjee MishraSunil Kumar Mukherjee
Feb 17, 2015·Chembiochem : a European Journal of Chemical Biology·José A Reyes-DariasAlfredo Berzal-Herranz
Jul 24, 2012·Virus Research·José A Reyes-DariasAlfredo Berzal-Herranz

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Methods Mentioned

BETA
electrophoresis
transfection
PCR
in vitro transcription
in
ex vivo transcription

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