Arkadiusz Kazula

Ribozymes and DNAzymes – molecular structure, mechanism action and application in gene therapy
2018-04-06

The discovery of catalytic nucleic acids RNA provided scientists with valuable tools for the identification of new therapies for several untreated diseases through down regulation or modulation of endogenous gene expression involved in these ailments. Ribozymes, can be mostly used to down-regulate (by RNA cleavage) or repair (by RNA trans-splicing) unwanted gene expression involved in disease. Because of their high specificity, wide range of target selection and action before protein translation, the different classes of both natural and artificial ribozymes have been claimed to be used as specific suppressors of gene functions with the additional aim of validating disease-related genes as potential targets for new therapeutic interventions. However, the lack of suitable delivery systems in to target cells still hampers the clinical development of ribozyme-based therapeutics. Introduction to different types of ribozymes with a special focus on the hammerhead and hairpin ribozyme, major challenges in the process of developing ribozymes for medical purposes will be described in the present review. DNAzymes, derived by in vitro selection processes are also able to bind and cleave RNA targets and therefore down-regulate gene expression in therapy. Subsequently, examples of ribozymes and DNAzymes applications in animal models for various diseases including cancer, viral infections, rheumatoid arthritis and cardiovascular diseases will be given. This review briefly summarizes the ever increasing evidence to the use of ribozymes as innovative nucleic acid-based enzymes along with their classifications, their mechanism in initiating catalytic effect and their potential pharmaceutical applications and their roles in gene function study and in target validation.

Keywords: catalytic nucleic acids, ribozyme, DNAzyme, hammerhead ribozyme, hairpin ribozyme

© Farm Pol, 2018, 74(4): 223-246