Aptamers: an emerging class of therapeutics.
Numerous nucleic acid ligands, also termed decoys or aptamers, have been developed during the past 15 years that can inhibit the activity of many pathogenic proteins. Two of them, Macugen and E2F decoy, are in phase III clinical trials. Several properties of aptamers make them an attractive class of therapeutic compounds. Their affinity and specificity for a given protein make it possible to isolate a ligand to virtually any target, and adjusting their bioavailability expands their clinical utility. The ability to develop aptamers that retain activity in multiple organisms facilitates preclinical development. Antidote control of aptamer activity enables safe, tightly controlled therapeutics. Aptamers may prove useful in the treatment of a wide variety of human maladies, including infectious diseases, cancer, and cardiovascular disease. We review the observations that facilitated the development of this emerging class of therapeutics, summarize progress to date, and speculate on the eventual utility of such agents in the clinic.
Nimjee
Shahid M
SM
University Program of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA. nimje001@mc.duke.edu
Rusconi
Christopher P
CP
Sullenger
Bruce A
BA
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000931:Antidotes / Q000627:therapeutic use*; D052157:Aptamers, Nucleotide; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D017326:Clinical Trials, Phase III as Topic; D004268:DNA-Binding Proteins / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000627:therapeutic use*; D015723:Gene Library; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D009841:Oligonucleotides / Q000235:genetics / Q000627:therapeutic use*; D014157:Transcription Factors / Q000627:therapeutic use*; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
D000890:Anti-Infective Agents; D000931:Antidotes; D052157:Aptamers, Nucleotide; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D015507:Drugs, Investigational; D009841:Oligonucleotides; C094103:TFDP2 protein, human; D014157:Transcription Factors; D014764:Viral Proteins; C495058:pegaptanib