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Molecules 2010, 15(7), 4757-4772; doi:10.3390/molecules15074757
Article

Inhibition of HIV-1 Replication and Dimerization Interference by Dual Inhibitory RNAs

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Received: 31 May 2010; in revised form: 28 June 2010 / Accepted: 1 July 2010 / Published: 7 July 2010
(This article belongs to the Special Issue Catalytic Nucleic Acids)
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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.
Keywords: Ribozymes; antisense RNAs; HIV-1 RNA dimerization; anti-HIV RNAs Ribozymes; antisense RNAs; HIV-1 RNA dimerization; anti-HIV RNAs
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Sánchez-Luque, F.J.; Reyes-Darias, J.A.; Puerta-Fernández, E.; Berzal-Herranz, A. Inhibition of HIV-1 Replication and Dimerization Interference by Dual Inhibitory RNAs. Molecules 2010, 15, 4757-4772.

AMA Style

Sánchez-Luque FJ, Reyes-Darias JA, Puerta-Fernández E, Berzal-Herranz A. Inhibition of HIV-1 Replication and Dimerization Interference by Dual Inhibitory RNAs. Molecules. 2010; 15(7):4757-4772.

Chicago/Turabian Style

Sánchez-Luque, Francisco J.; Reyes-Darias, José A.; Puerta-Fernández, Elena; Berzal-Herranz, Alfredo. 2010. "Inhibition of HIV-1 Replication and Dimerization Interference by Dual Inhibitory RNAs." Molecules 15, no. 7: 4757-4772.



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