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The Molecular Basis of Bladder Cancer and Prospects for Gene Therapy Using Hammerhead Ribozymes
Published in Eric Wickstrom, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Eric J. Small, Mohammed Kashani-Sabet, David Y. Bouffard, Kevin J. Scanlon
The presumed role of Η-ras expression in bladder tumorigenesis has been the basis for the experimental suppression of H-ras gene expression. At the molecular level, this suppression has entailed the use of antisense molecules or hammerhead ribozymes. Ribozymes are catalytic RNAs that bind to an RNA sequence selectively and cleave at predetermined sequences. Ribozymes were initially discovered in the self splicing of Tetrahymena ribosomal RNA (Grabowski et al., 1981) and in Escherichia coli RNase Ρ (Guerrier-Takada et al., 1983). The characterization of a potentially trans-acting RNA was achieved by Forster and Symons (1987) in the virusoid from lucerne transient streak virus. This ribozyme was termed hammerhead owing to its secondary structure. The consensus sequences for target RNA cleavage of the ribozyme were initially defined by Haseloff and Gerlach (1988). Thus, hammerhead ribozymes were shown to cleave 3' to XUN sequences, where X is any base and Ν is A, C, or U. An example of a target sequence is the GUC sequence of the mutated codon 12 of the Η-ras oncogene mRNA (Figure 1). The ribozyme molecule consists of a catalytic core (including the hammerhead domain) and three helices. Two of these helices (stems I and III) act as flanking sequences which confer specificity by binding to the target message in antisense fashion. Ribozymes therefore have the potential advantage of acting as antisense RNAs as well as of cleaving the target RNA directly. The biochemistry of hammerhead ribozymes has been extensively reviewed elsewhere (Bratty et al., 1993; Kashani-Sabet and Scanlon, 1995).
Virus-associated ribozymes and nano carriers against COVID-19
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2021
Beyza Dönmüş, Sinan Ünal, Fatma Ceren Kirmizitaş, Nelisa Türkoğlu Laçin
Seven catalytic RNAs have been identified to date that occur naturally. Ribozymes are divided into three groups in terms of function and shape: self-splicing introns, ribonuclease P (RNase P) and small catalytic RNAs [61]. The hammerhead, hairpin, Neurospora Varkud satellite (VS) and hepatitis delta virus (HDV) ribozymes are small RNAs of 50–150 nucleotides that perform site-specific self-cleavage [63]. They are found in RNA genomes as viral, virusoid or satellite a subviral agent and integrate into the genome by rolling ring replication [62].