Aptamers: An Emerging Class of Therapeutics

Abstract

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.

RNA-binding protein nucleolin in disease

“…Aptamers are short, stable DNA or RNA molecules that can target specific cellular and extracellular targets with high affinity. 131,132 The aptamer AS1411, also known as AGRO100, a 26-mer unmodified guanosine (G)-rich oligonucleotide [5'-d(GGT GGT GGT GGT TGT GGT GGT GGT GG)-3'], is among the aptamers most extensively studied and used. Nucleolin has high affinity for AS1411, in agreement with the strong binding of nucleolin to G-quadruplex DNA sequences.…”

Novel Cell type-specific aptamer-siRNA delivery system for HIV-1 therapy

“…Because aptamers are capable of binding with high specificity to their ligands at low nano-to picomolar dissociation constants they can be used as molecular drugs for both basic research and clinical purposes 44,45,46,47,48 .…”

Aptamer-based therapeutics and their potential in radiopharmaceutical design

“…Aptamers chief advantage lies on their technical versatility and applicability to a wide array of target molecules. It is expected that certain applications that use antibodies will gradually be used in conjunction or replaced by aptamers because of their inherent characteristics (Nimjee, 2005). The question now remains whether these advantages are unique enough to prompt researchers to overcome some of the daunting disadvantages and establish aptamers as diagnostic and therapeutic agents in the clinic.…”