title: DNA enzymes as potential therapeutics: towards clinical application of 10-23 DNAzymes.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences , 8 Lavrentiev Avenue, Novosibirsk 630090 , Russia fokina@niboch.nsc.ru.
authors.forename: Alesya A
authors.initials: AA
authors.lastname: Fokina
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Stetsenko
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: François
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D021881:DNA, Catalytic / Q000235:genetics* / Q000627:therapeutic use*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000627:therapeutic use; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D021881:DNA, Catalytic; D016376:Oligonucleotides, Antisense; D016337:RNA, Catalytic; D034741:RNA, Small Interfering; D004247:DNA
keywords: 10-23 DNAzyme; RNA cleavage; anti-cancer drug; antibacterial; antisense; antiviral; clinical trial; deoxyribozyme; gene expression downregulation; oligonucleotide