DNA enzymes as potential therapeutics: towards clinical application of 10-23 DNAzymes

Abstract

Introduction: Ongoing studies on the inhibition of gene expression at the mRNA level have identified several types of specific inhibitors such as antisense oligonucleotides, small interfering RNA, ribozymes and DNAzymes (Dz). After its discovery in 1997, the 10-23 Dz (which can cleave RNA efficiently and site-specifically, has flexible design, is independent from cell mechanisms, does not require expensive chemical modifications for effective use in vivo) has been employed to downregulate a range of therapeutically important genes. Recently, 10-23 Dzs have taken their first steps into clinical trials.

Areas covered: This review focuses predominantly on Dz applications as potential antiviral, antibacterial, anti-cancer and anti-inflammatory agents as well as for the treatment of cardiovascular disease and diseases of CNS, summarizing results of their clinical trials up to the present day.

Expert opinion: In comparison with antisense oligonucleotides and small interfering RNAs, Dzs do not usually show off-target effects due to their high specificity and lack of immunogenicity in vivo. As more results of clinical trials carried out so far are gradually becoming available, Dzs may turn out to be safe and well-tolerated therapeutics in humans. Therefore, there is a good chance that we may witness a deoxyribozyme drug reaching the clinic in the near future.

Keywords:

• 10-23 DNAzyme
• antibacterial
• anti-cancer drug
• antisense
• antiviral
• clinical trial
• deoxyribozyme
• gene expression downregulation
• oligonucleotide
• RNA cleavage

Acknowledgements

The authors would like to thank Michael J Gait for critical reading of the manuscript.

Declaration of interest

This work was partly carried out with support of the Russian government for research projects implemented under supervision of world-leading scientists (agreement No. 14.B25.31.0028 with S Altman as a leading scientist) and RFBR grant No. 15-03-06331 to DA Stetsenko Funding was also received from the Institute of Chemical Biology and Fundamental Medicine SB RAS and the Centre De Researche Saint-Antoine INSERM-UPMC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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