title: Inhibition of HIV-1 gp41 expression with hammerhead ribozymes.
abstract: 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.
authors.affiliation: Institute of Bioorganic Chemistry, The Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Fedoruk-Wyszomirska
authors.affiliation: Department of Computational Biology, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznań, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Szymański
authors.affiliation: Institute of Bioorganic Chemistry, The Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Głodowicz
authors.affiliation: 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.
authors.forename: Marta
authors.initials: M
authors.lastname: Gabryelska
authors.affiliation: Institute of Bioorganic Chemistry, The Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: Eliza
authors.initials: E
authors.lastname: Wyszko
authors.affiliation: 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. drbillestrin@hotmail.com Jan.Barciszewski@ibch.poznan.pl.
authors.forename: William J
authors.initials: WJ
authors.lastname: Estrin
authors.affiliation: Institute of Bioorganic Chemistry, The Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland drbillestrin@hotmail.com Jan.Barciszewski@ibch.poznan.pl.
authors.forename: Jan
authors.initials: J
authors.lastname: Barciszewski
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D015700:HIV Envelope Protein gp41 / Q000096:biosynthesis* / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism*
chemical_list: D015700:HIV Envelope Protein gp41; D016337:RNA, Catalytic; C514787:gp41 protein, Human immunodeficiency virus 1; C427204:hammerhead ribozyme
keywords: HIV-1; catalytic RNA; gp41; hammerhead ribozymes; stabilized ribozymes