Inhibition of human immunodeficiency virus type 1 replication by nuclear chimeric anti-HIV ribozymes in a human T lymphoblastoid cell line

Human Gene Therapy
A MichienziI Bozzoni

Abstract

Human immunodeficiency virus (HIV) infection represents one of the most challenging systems for gene therapy. Thanks to the extended knowledge of the molecular biology of the HIV life cycle, many different strategies have been developed including transdominant modifications of HIV proteins, RNA decoys, antisense RNA, ribozymes, and intracellular antibody fragments. In this paper, we have tested in a human T lymphoblastoid cell line the antiviral activity of ribozymes specifically designed to co-localize inside the nucleus with the Rev pre-mRNA before it is spliced and transported to the cytoplasm. This result was obtained by inserting the ribozyme in the spliceosomal U1 small nuclear RNA (snRNA) and in a derivative that has perfect complementarity with the 5' splice site of the Rev pre-mRNA. These ribozymes were tested in human T cell clones and were shown to be very efficient in inhibiting viral replication. Not only were the p24 levels in the culture medium drastically reduced but so were the intracellular HIV transcripts. Control disabled ribozymes enabled us to show the specificity of the ribozyme activity. Therefore, these constructs have potential utility for gene therapy of HIV-1 infection.

References

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Citations

Oct 18, 2000·Advanced Drug Delivery Reviews·J J Rossi
Dec 12, 2001·Vaccine·B S Peters
Nov 20, 1998·Current Opinion in Biotechnology·P J WelchF Wong-Staal
May 23, 2001·The Biochemical Journal·M Dundr, T Misteli
Dec 12, 2001·HIV Medicine·N Dorman, A M Lever
Apr 3, 2001·Molecular and Cellular Biology·S A BeckleyD W Rowe
Apr 5, 2001·Sexually Transmitted Infections·A M Lever
Feb 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Michela Alessandra DentiIrene Bozzoni
Dec 1, 2001·Expert Opinion on Biological Therapy·N DüzgünesM C Pedroso de Lima
Jul 27, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Michela Alessandra DentiIrene Bozzoni
Sep 2, 2000·The Journal of Biological Chemistry·L GormanR Kole
Sep 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·L ContiS Gessani

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