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  Endogenous expression of a high-affinity pseudoknot RNA aptamer suppresses replication of HIV-1

Chaloin, L., Lehmann, M. J., Sczakiel, G., & Restle, T. (2002). Endogenous expression of a high-affinity pseudoknot RNA aptamer suppresses replication of HIV-1. Nucleic Acids Research, 30(18): 1, pp. 4001-4008. Retrieved from http://nar.oupjournals.org/cgi/reprint/30/18/4001.

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Genre: Journal Article
Alternative Title : Nucl. Acids Res.

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 Creators:
Chaloin, Laurent1, Author
Lehmann, Maik Jörg, Author
Sczakiel, Georg, Author
Restle, Tobias2, Author           
Affiliations:
1Max Planck Institute of Molecular Physiology, Max Planck Society, ou_1753286              
2Abt. III: Physikalische Biochemie, Max Planck Institute of Molecular Physiology, Max Planck Society, ou_1753289              

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 Abstract: Aptamers, small oligonucleotides derived from an in vitro evolution process called SELEX, are promising therapeutic and diagnostic agents. Although very effective in vitro, only a few examples are available showing their potential in vivo. We have analyzed the effect of a well characterized pseudoknot RNA aptamer selected for tight binding to human immunodeficiency virus (HIV) type 1 reverse transcriptase on HIV replication. Transient intracellular expression of a chimeric RNA consisting of the human initiator tRNA(Met) (tRNA(Meti))/aptamer sequence in human 293T cells showed inhibition of HIV particle release by >75% when the cells were co-transfected with proviral HIV-1 DNA. Subsequent virus production of human T-lymphoid C8166 cells, infected with viral particles derived from co- transfected 293T cells, was again reduced by >75% as compared with the control. As the observed effects are additive, in this model for virus spread, the total reduction of HIV particle formation by transient intracellular expression of the pseudoknot RNA aptamer amounts to >95%. Low-dose HIV infection of human T cells stably expressing the aptamer did not show any virus replication over a period of 35 days. This is the first example of an RNA aptamer selected against a viral enzyme target to show powerful antiviral activity in HIV-1-permissive human T-lymphoid cell lines.

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Language(s): eng - English
 Dates: 2002-09-15
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 14475
URI: http://nar.oupjournals.org/cgi/reprint/30/18/4001
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Title: Nucleic Acids Research
  Alternative Title : Nucl. Acids Res.
Source Genre: Journal
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Pages: - Volume / Issue: 30 (18) Sequence Number: 1 Start / End Page: 4001 - 4008 Identifier: -