A Brief History of Genetic Therapy: Gene Therapy, Antisense Technology, and Genomics
Eric Wickstrom in Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Catalytic RNAs are RNA structures capable of cleaving covalent bonds in an RNA molecule. Catalytic RNAs were first described by Cech's laboratory (Zaug et al., 1980; Cech et al., 1981; Kruger et al., 1982) and Altman etal. (Guerrier-Takada et al., 1983). Cech described the catalytic removal of introns in the pre-rRNA of the ciliated protozoan, Tetrahymena thermophila. The term "ribozyme" describes RNA (ribonucleic acid) molecules with catalytic properties analogous to enzymes, as explained by Kruger et al. (1982), Because the IVS RNA is not an enzyme but has some enzyme-like characteristics, we call it a ribozyme, an RNA molecule that has the intrinsic ability to break and form covalent bonds.
Biochemistry
Sarah Armstrong, Barry Clifton, Lionel Davis in Primary FRCA in a Box, 2019
Macromolecular biological catalysts that accelerate chemical reactions whilst remaining themselves unchanged Almost all metabolic processes need enzymes to occur at rates fast enough to sustain lifeMost are globular proteins, much larger than their substrates. A few are catalytic RNA molecules (ribozymes)May be highly specific for a given substrate – specificity comes from their unique three-dimensional structuresSensitive to pH and temperature change
Gene Therapy for Lung Cancer
Kenneth L. Brigham in Gene Therapy for Diseases of the Lung, 2020
Several antisense approaches have been investigated. One approach is through the use of antisense oligonucleotides, in which the phosphodiester backbone is modified to methylphosphonate or phosphorothioate to reduce degradation by nucleases. These modified antisense oligonucleotides can enter tumor cells by endocytosis and form DNA-RNA duplexes with endogenous sense mRNA, inhibiting translation. Another approach to inactivating mRNA is via ribozymes. Ribozymes are essentially antisense oligonucleotides that contain RNase active sites. A ribozyme possessing this activity allows catalytic gene ablation by sequence-specific cleavage of the target transcript. A third approach is to use plasmids or viral vectors for transferring an open reading frame fragment of the desired gene oriented backwards (3' to 5') behind a powerful promoter, resulting in the production of an antisense RNA. Antisense RNA transcribed from these constructs form a RNA duplex with sense mRNA inhibiting translation (89).
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
GlmS ribozyme was discovered as an RNA domain that catalyses region-specific RNA cut in the presence of a small molecule metabolite called glucosamine-6-phosphate (GlcN6P) [99]. The RNA domain is the part of mRNA, encoding the essential enzyme that expresses GlcN6P in gram-positive bacteria [100]. Riboswitch motifs act as a biosensor sensitive to intracellular concentrations of certain metabolites. GlmS ribozyme is a riboswitch motif preserved in a large number of gram-positive bacteria [101]. Also, the GlmS ribozyme is the first self-degrading RNA using an exogenous acid-based catalyst [102]. Figure 8 shows the secondary structure of a trans-cleavage GlmS ribozyme.
Nucleic acid therapeutics: a focus on the development of aptamers
Published in Expert Opinion on Drug Discovery, 2021
Swati Jain, Jaskirat Kaur, Shivcharan Prasad, Ipsita Roy
Another modification of ribozyme is ‘aptazyme’, also known as allosteric ribozyme, which has a ligand-binding site and a catalytic site for nucleic acids [57]. Aptazymes act as allosteric catalysts; when ligands bind to the aptazyme, conformational changes occur in the ligand-binding domain leading to modulation of catalytic activity [58,59,61]. Aptazymes are small (~ 100 nt) in size and have been engineered to bind to proteins and peptides, as well as small molecules [60–62]. Allosteric activation of aptazymes by specific molecules/cofactors enables them to function as sensors, with appropriate labels for quantitative read-outs [61,63,64].
The application of gene silencing in proteomics: from laboratory to clinic
Published in Expert Review of Proteomics, 2018
Maura Brioschi, Cristina Banfi
Ribozymes catalyze highly sequence-specific reactions determined by RNA–RNA interactions, between the ribozyme and its target gene, which led to target RNA cleavage [21]. RNAi are instead double strands RNAs able to induce degradation of specific mRNA sequences, as described below in detail.
Related Knowledge Centers
- Catalysis
- DNA
- Enzyme
- Gene Expression
- Ribosome
- Rna
- Rna Splicing
- Rna World
- Directed Evolution
- Translation