Aptamers: A Review of Their Chemical Properties and Modifications for Therapeutic Application

Abstract

Aptamers are short, single-stranded oligonucleotides that bind to specific target molecules. The shape-forming feature of single-stranded oligonucleotides provides high affinity and excellent specificity toward targets. Hence, aptamers can be used as analogs of antibodies. In December 2004, the US Food and Drug Administration approved the first aptamer-based therapeutic, pegaptanib (Macugen), targeting vascular endothelial growth factor, for the treatment of age-related macular degeneration. Since then, however, no aptamer medication for public health has appeared. During these relatively silent years, many trials and improvements of aptamer therapeutics have been performed, opening multiple novel directions for the therapeutic application of aptamers. This review summarizes the basic characteristics of aptamers and the chemical modifications available for aptamer therapeutics.

Keywords: RNA therapeutics; aptamer; chemical modifications; conformational plasticity.

Figure 1

Overall structure of known aptamer–protein complexes with electrostatic surface potential [5]. The RNA aptamer is represented by a yellow ball-and-stick model. (A) Aptamer–thrombin complex at 1.8 Å resolution [13]. (B) Aptamer–nuclear factor-κB complex at 2.45 Å resolution [11]. (C) Aptamer–MS2 coat protein complex at 2.8 Å resolution [12]. (D) Aptamer–Fc region of human IgG1 (hFc1) complex at 2.15 Å resolution [16]. Blue areas: positively charged; red areas: negatively charged.

Figure 2

Chemical structure of a polynucleotide element. Modifications at the indicated positions are shown. OMe: O-methylation, LNA: locked nucleic acid, PEG: polyethylene glycol.