Development of ribozyme-based gene-inactivations; the example of the hepatitis delta virus ribozyme.
The development of gene-inactivation systems is an active and important field for both functional genomics and gene therapy. Towards this end, ribozymes (i.e. RNA enzymes), that specifically recognize and subsequently catalyze the cleavage of other target RNA molecules, are attractive molecular tools. Ribozymes represent an interesting alternative to the RNA interference (RNAi) approach for gene inactivation, especially given the fact that RNAi seems to trigger an immunological response and has demonstrated off-target effects. However, the design and optimization of a ribozyme-based gene-inactivation system is not a straightforward procedure. Several aspects need to be considered in the experimental design in order to provide a suitable suppression system. In this review we present the advances in this domain made available from work using the hepatitis delta virus (HDV) ribozyme as a cis-acting RNA motif in molecular biology, as well as a trans-acting molecular scissor for the development of a gene-inactivation system. This HDV ribozyme technology possesses several unique features that are all related to the fact that it is the only catalytic cleaving RNA motif that has been discovered in humans.
Asif-Ullah
M
M
RNA Group/Groupe ARN, Département de Biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, J1H 5N4, Canada.
Lévesque
Michel
M
Robichaud
Gilles
G
Perreault
Jean-Pierre
JP
D001483:Base Sequence; D015195:Drug Design; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends; D003698:Hepatitis Delta Virus / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D034622:RNA Interference; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*
D016337:RNA, Catalytic