Nucleic Acid Aptamers: New Methods for Selection, Stabilization, and Application in Biomedical Science

Abstract

The adoption of oligonucleotide aptamer is well on the rise, serving an ever increasing demand for versatility in biomedical field. Through the SELEX (Systematic Evolution of Ligands by EXponential enrichment), aptamer that can bind to specific target with high affinity and specificity can be obtained. Aptamers are single-stranded nucleic acid molecules that can fold into complex threedimensional structures, forming binding pockets and clefts for the specific recognition and tight binding of any given molecular target. Recently, aptamers have attracted much attention because they not only have all of the advantages of antibodies, but also have unique merits such as thermal stability, ease of synthesis, reversibility, and little immunogenicity. The advent of novel technologies is revolutionizing aptamer applications. Aptamers can be easily modified by various chemical reactions to introduce functional groups and/or nucleotide extensions. They can also be conjugated to therapeutic molecules such as drugs, drug containing carriers, toxins, or photosensitizers. Here, we discuss new SELEX strategies and stabilization methods as well as applications in drug delivery and molecular imaging.

Ras ssDNA aptamer inhibits vascular smooth muscle cell proliferation and migration through MAPK and PI3K pathways

“…Aptamers with high affinity and specificity have been developed to target peptides, proteins, drugs, organic and inorganic molecules and even whole cells (7)(8)(9). Accumulating evidence has indicated that certain aptamers showed great therapeutic efficacy both in vitro and in vivo.…”

“…Using the systematic evolution of ligands by exponential enrichment (SELEX) technique, several aptamers with high affinity and specificity for target proteins were previously selected from a library of randomized sequences in vitro, including single-stranded DNA (ssDNA) or RNA oligonucleotides (7)(8)(9). For instance, Bell et al (10) developed an oligonucleotide designated as NX1838 (2'-fluoropyrimidine, RNA-based oligonucleotide/40-kDa-PEG) that inhibited vascular endothelial growth factor 165 (VEGF165)-mediated cell response in vitro by directly targeting the VEGF165 factor.…”

Neutralization of Staphylococcal Enterotoxin B by an Aptamer Antagonist

“…However, therapeutic aptamers alone are not sufficiently stable for in vivo delivery, so they are usually modified or conjugated to vehicles that are resistant to nucleases to improve their residence time (33). Considering that PEGylation is one of the most commonly used modifications of aptamers (34,35), we analyzed the therapeutic effects of PEGylated A11 in vivo.…”

Aptamer Oligonucleotides: Novel Potential Therapeutic Agents in Autoimmune Disease

“…In this process, a synthesized mirror image form (eg, d-polypeptide) of the target molecule (eg, l-polypeptide) is used as the target to screen aptamers by in vitro selection from a synthetic natural d-oligonucleotide library at first. Then, the selected d-aptamers are synthesized as Spiegelmers (l-aptamers), which can bind to the original target molecules (eg, l-polypeptide) using enantiomeric l-ribonucleotides [16]. Vater et al reported a mixed 39-mer antiglucagon DNA/RNA-Spiegelmer modified with 2¢-oxygens on the sugar backbone and conjugated them with PEG at the 5¢-end (NOX-G15; Noxxon Pharma).…”