Modulation of gene expression by antisense and antigene oligodeoxynucleotides and small interfering RNA.
Antisense oligodeoxynucleotides, triplex-forming oligodeoxynucleotides and double-stranded small interfering RNAs have great potential for the treatment of many severe and debilitating diseases. Concerted efforts from both industry and academia have made significant progress in turning these nucleic acid drugs into therapeutics, and there is already one FDA-approved antisense drug in the clinic. Despite the success of one product and several other ongoing clinical trials, challenges still exist in their stability, cellular uptake, disposition, site-specific delivery and therapeutic efficacy. The principles, strategies and delivery consideration of these nucleic acids are reviewed. Furthermore, the ways to overcome the biological barriers are also discussed so that therapeutic concentrations at their target sites can be maintained for a desired period.
Mahato
Ram I
RI
University of Tennessee Health Science Center, Department of Pharmaceutical Sciences, 26 South Dunlap Street, Feurt Bldg RM 406, Memphis, TN 38163, USA. rmahato@utmem.edu
Cheng
Kun
K
Guntaka
Ramareddy V
RV
D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004337:Drug Carriers; D005786:Gene Expression Regulation; D020868:Gene Silencing; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009690:Nucleic Acid Conformation / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D034622:RNA Interference; D012326:RNA Splicing / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D004337:Drug Carriers; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C051802:triplex DNA; D004247:DNA