PMID: 7544887Aug 11, 1995Paper

Target sequence-specific inhibition of HIV-1 replication by ribozymes directed to tat RNA

Nucleic Acids Research
L Q SunG P Symonds

Abstract

The structural motif formed between a hammerhead ribozyme and its substrate consists of three RNA double helices in which the sequence 5' to the XUY is termed helix I and the sequence 3' to the XUY helix III. Two hammerhead ribozymes targeted to the tat gene of HIV-1SF2 were designed to study target specificity and the potential effect of helix I mismatch on ribozyme efficacy both in vitro and in vivo. The first ribozyme (Rz1) targeted to the 5' splicing region of the tat gene was designed to cleave GUC*A. In HIV-1IIIB the A is changed to a G. The second ribozyme (Rz2) was targeted to the translational initiation region of the tat gene which is highly conserved among a variety of HIV-1 isolates, including both HIV-1SF2 and HIV-1IIIB. In vitro cleavage studies demonstrated that Rz1 efficiency cleaved HIV-1SF2 substrate RNA, but not HIV-1IIIB, presumably due to the base change from A to G. In contrast, Rz2 cleaved HIV-1SF2 or HIV-1IIIB substrate with equal efficiency. Both ribozymes were cloned into the 3' untranslated region of the neomycin gene (neo) within the pSV2neo vector and transfected into the SupT1 human CD4+ T cell line. Following selection, stable transfectants were challenged with either HIV-1SF2 or HIV-1IIIB virus. ...Continue Reading

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Citations

Jan 1, 1997·Journal of Cancer Research and Clinical Oncology·M Y ChangH S Liu
Jun 1, 1997·Molecular Biotechnology·L Q SunG Symonds
Aug 1, 1997·Molecular Biotechnology·A Menke, G Hobom
Jul 17, 1999·Immunopharmacology·G BieseckerR A Bendele
Dec 1, 1996·Trends in Genetics : TIG·L A Couture, D T Stinchcomb
Aug 3, 2001·Brain Research. Molecular Brain Research·J R SubramaniamJ H Neale
Nov 10, 2000·Advanced Drug Delivery Reviews·L A Phylactou
Feb 17, 2009·Nature Medicine·Ronald T MitsuyasuDavid A Cooper
Jan 1, 1996·Antisense & Nucleic Acid Drug Development·K K SinghG Krupp
Mar 25, 1998·Antisense & Nucleic Acid Drug Development·L A WrightP Kearney
May 9, 2001·Nucleic Acids Research·A A MirP Hendry
Apr 1, 1997·European Journal of Biochemistry·K R BirikhF Eckstein
May 17, 2003·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·David SteeleGarrett A Soukup
Dec 1, 2001·Expert Opinion on Biological Therapy·N DüzgünesM C Pedroso de Lima
Jul 1, 2011·Stem Cells International·Ronald T MitsuyasuGeoff P Symonds
Aug 5, 2003·The Journal of Gene Medicine·Greg FanningGeoff Symonds
Sep 25, 2009·The Journal of Gene Medicine·John M MurrayGeoff P Symonds
Apr 17, 2003·FEMS Microbiology Reviews·Elena Puerta-FernándezAlfredo Berzal-Herranz
Sep 10, 1998·Biochemical and Biophysical Research Communications·L A PhylactouM W Kilpatrick
Sep 12, 2002·Expert Opinion on Therapeutic Targets·John Goodchild
Aug 1, 2015·Viruses·Gero HütterGeoff Symonds
Aug 23, 2006·Molecular and Cellular Biochemistry·Jens-Uwe PeterDiego J Walther
Dec 23, 2020·Human Gene Therapy·Tatjana I CornuToni Cathomen
Jan 13, 2018·Chemical Reviews·Alicia J AngelbelloMatthew D Disney
Oct 23, 1997·American Journal of Human Genetics·K F Kozarsky, L A Couture

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