Abstract
(apto: âto fitâ& mer: âsmallest unit of repeating structureâ). Aptamers are single stranded folded oligonucleotides and peptide that bind to molecular (protein) targets with high affinity and specificity.In addition to target validation and research applications, aptamers are being developed as therapeutic agents. A number of aptamers have completed various stages of pre-clinical development, ranging from pharmacokinetic analysis, characterization of biological efficacy in cellular and animal disease models, and safety assessment. In particular, one aptamer, targeting vascular endothelial growth factor (VEGF), has completed phase III clinical trials for age-related macular degeneration (AMD), a leading cause of blindness. Aptamers constitute one of four classes of oligonucleotide reagents, the others being antisense oligonucleotides, ribozymes and small interfering RNAs (siRNAs)Â SiRNAs, discovered less than a decade ago, have generated tremendous interest as potential therapeutic agents, and several compounds have already entered clinical trials. Ribozymes and antisense oligonucleotides have been under study for more than two decades, but to date only one commercially available therapeutic agent, fomivirsen (Vitravene,Novartis), an antisense oligonucleotide used to treat cytomegalovirus retinitis, has resulted from these approaches. Difficulties with the development of these agents include instability in biological media and, more importantly, a requirement to cross cellular membranes in order to exert their therapeutic actions. Like other oligonucleotide agents, aptamers are not bioavailable when administered orally and do not readily cross cell membranes.
