Therapeutic nucleic acids: current clinical status.
Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are simple linear polymers that have been the subject of considerable research in the last two decades and have now moved into the realm of being stand-alone therapeutic agents. Much of this has stemmed from the appreciation that they carry out myriad functions that go beyond mere storage of genetic information and protein synthesis. Therapy with nucleic acids either uses unmodified DNA or RNA or closely related compounds. From both a development and regulatory perspective, they fall somewhere between small molecules and biologics. Several of these compounds are in clinical development and many have received regulatory approval for human use. This review addresses therapeutic uses of DNA based on antisense oligonucleotides, DNA aptamers and gene therapy; and therapeutic uses of RNA including micro RNAs, short interfering RNAs, ribozymes, RNA decoys and circular RNAs. With their specificity, functional diversity and limited toxicity, therapeutic nucleic acids hold enormous promise. However, challenges that need to be addressed include targeted delivery, mass production at low cost, sustaining efficacy and minimizing off-target toxicity. Technological developments will hold the key to this and help accelerate drug approvals in the years to come.
Department of Health Sciences, College of Medicine, Nursing and Health Sciences, Fiji National University, Suva, Fiji.
Kannan
0000-0003-3811-6503
K
Sridharan
Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai, India.
Nithya Jaideep
NJ
Gogtay
D052157:Aptamers, Nucleotide / Q000627:therapeutic use; D004247:DNA / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D035683:MicroRNAs / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D012313:RNA / Q000627:therapeutic use*; D016337:RNA, Catalytic / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000627:therapeutic use
D052157:Aptamers, Nucleotide; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D016337:RNA, Catalytic; D034741:RNA, Small Interfering; D012313:RNA; D004247:DNA
RNA decoys; antisense oligonucleotides; aptamers; gene therapy; ribozymes