Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (205K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (36)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Chaloin, L.
Right arrow Articles by Restle, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chaloin, L.
Right arrow Articles by Restle, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2002, Vol. 30, No. 18 4001-4008
© 2002 Oxford University Press

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

Laurent Chaloin, Maik Jörg Lehmann1, Georg Sczakiel2 and Tobias Restle*

Max-Planck-Institut für molekulare Physiologie, Abteilung Physikalische Biochemie, Otto Hahn Straße 11, 44227 Dortmund, Germany, 1 Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany and 2 Institut für Molekulare Medizin, Medizinische Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany

*To whom correspondence should be addressed. Tel: +49 231 133 2364; Fax: +49 231 133 2398; Email: tobias.restle{at}mpi-dortmund.mpg.de

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 tRNAMet (tRNAMeti)/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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
D. Michalowski, R. Chitima-Matsiga, D. M. Held, and D. H. Burke
Novel bimodular DNA aptamers with guanosine quadruplexes inhibit phylogenetically diverse HIV-1 reverse transcriptases
Nucleic Acids Res., December 1, 2008; 36(22): 7124 - 7135.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. D. Kissel, D. M. Held, R. W. Hardy, and D. H. Burke
Active site binding and sequence requirements for inhibition of HIV-1 reverse transcriptase by the RT1 family of single-stranded DNA aptamers
Nucleic Acids Res., August 1, 2007; 35(15): 5039 - 5050.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
D. M. Held, J. D. Kissel, S. J. Thacker, D. Michalowski, D. Saran, J. Ji, R. W. Hardy, J. J. Rossi, and D. H. Burke
Cross-Clade Inhibition of Recombinant Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus SIVcpz Reverse Transcriptases by RNA Pseudoknot Aptamers
J. Virol., May 15, 2007; 81(10): 5375 - 5384.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
W. James
Aptamers in the virologists' toolkit
J. Gen. Virol., February 1, 2007; 88(2): 351 - 364.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
A. Mescalchin, W. Wunsche, S. D. Laufer, D. Grohmann, T. Restle, and G. Sczakiel
Specific binding of a hexanucleotide to HIV-1 reverse transcriptase: a novel class of bioactive molecules
Nucleic Acids Res., November 14, 2006; 34(19): 5631 - 5637.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. M. Held, J. D. Kissel, D. Saran, D. Michalowski, and D. H. Burke
Differential Susceptibility of HIV-1 Reverse Transcriptase to Inhibition by RNA Aptamers in Enzymatic Reactions Monitoring Specific Steps during Genome Replication
J. Biol. Chem., September 1, 2006; 281(35): 25712 - 25722.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
L. V. Gening, S. A. Klincheva, A. Reshetnjak, A. P. Grollman, and H. Miller
RNA aptamers selected against DNA polymerase {beta} inhibit the polymerase activities of DNA polymerases beta and kappa.
Nucleic Acids Res., January 1, 2006; 34(9): 2579 - 2586.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
K. Hu, J. Beck, and M. Nassal
SELEX-derived aptamers of the duck hepatitis B virus RNA encapsidation signal distinguish critical and non-critical residues for productive initiation of reverse transcription
Nucleic Acids Res., August 16, 2004; 32(14): 4377 - 4389.
[Abstract] [Full Text] [PDF]

Home page
 RNAHome page
D. G. NICKENS, J. T. PATTERSON, and D. H. BURKE
Inhibition of HIV-1 reverse transcriptase by RNA aptamers in Escherichia coli
RNA, September 1, 2003; 9(9): 1029 - 1033.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.