Despite great progress in the treatment of AIDS, HIV-1 remains one of the major concerns as a human pathogen. One of the therapeutic strategies against viral infections is the application of catalytic ribonucleic acids (ribozymes) that can significantly reduce expression of a target gene by site-specific hydrolysis of its mRNA. In the present paper, we report a study on the activity of several variants of hammerhead ribozymes targeting a conserved region within mRNA encoding HIV-1 envelope glycoprotein gp41. On the basis of the data from in vitro assays and gene silencing in the cultured cells, we propose a new hammerhead ribozyme targeting the gp41-encoding sequence that can be potentially used as a therapeutic agent in AIDS treatment. Moreover, we demonstrate that the hydrolytic activity of the ribozyme in the intracellular environment cannot be inferred solely from the results of in vitro experiments.
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October 2015
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Research Article|
September 21 2015
Inhibition of HIV-1 gp41 expression with hammerhead ribozymes
Agnieszka Fedoruk-Wyszomirska
;
Agnieszka Fedoruk-Wyszomirska
*Institute of Bioorganic Chemistry, The Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland
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Maciej Szymański
;
Maciej Szymański
†Department of Computational Biology, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznań, Poland
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Paweł Głodowicz
;
Paweł Głodowicz
*Institute of Bioorganic Chemistry, The Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland
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Marta Gabryelska
;
Marta Gabryelska
*Institute of Bioorganic Chemistry, The Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland
‡The MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, U.K.
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Eliza Wyszko
;
Eliza Wyszko
*Institute of Bioorganic Chemistry, The Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland
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William J. Estrin
;
William J. Estrin
1
§Saint Francis Memorial Hospital, 900 Hyde Street, San Francisco, CA 94109, U.S.A.
║St. Mary's Medical Center, 450 Stanyan Street, San Francisco, CA 94117, U.S.A.
¶California Pacific Medical Center, 2333 Buchanan Street, San Francisco, CA 94115, U.S.A.
**Chinese Hospital, 845 Jackson Street, San Francisco, CA 94133, U.S.A.
1Correspondence may be addressed to either of these authors (email drbillestrin@hotmail.com or Jan.Barciszewski@ibch.poznan.pl).
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Jan Barciszewski
Jan Barciszewski
1
*Institute of Bioorganic Chemistry, The Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland
1Correspondence may be addressed to either of these authors (email drbillestrin@hotmail.com or Jan.Barciszewski@ibch.poznan.pl).
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Biochem J (2015) 471 (1): 53–66.
Article history
Received:
April 01 2015
Revision Received:
July 23 2015
Accepted:
July 24 2015
Accepted Manuscript online:
July 24 2015
Citation
Agnieszka Fedoruk-Wyszomirska, Maciej Szymański, Paweł Głodowicz, Marta Gabryelska, Eliza Wyszko, William J. Estrin, Jan Barciszewski; Inhibition of HIV-1 gp41 expression with hammerhead ribozymes. Biochem J 1 October 2015; 471 (1): 53–66. doi: https://doi.org/10.1042/BJ20150398
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