In vitroevolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies

Abstract

Nucleic acid aptamers are single-stranded DNA or RNA oligonucleotide sequences that bind to a specific target molecule with high affinity and specificity through their ability to adopt 3-dimensional structure in solution. Aptamers have huge potential as targeted therapeutics, diagnostics, delivery agents and as biosensors. However, aptamers composed of natural nucleotide monomers are quickly degraded in vivo and show poor pharmacodynamic properties. To overcome this, chemically-modified nucleic acid aptamers are developed by incorporating modified nucleotides after or during the selection process by Systematic Evolution of Ligands by EXponential enrichment (SELEX). This review will discuss the development of chemically-modified aptamers and provide the pros and cons, and new insights on in vitro aptamer selection strategies by using chemically-modified nucleic acid libraries.

Circular Bivalent Aptamers Enable in Vivo Stability and Recognition

“…Chemical modifications, including postselection modification and SELEX with modified oligonucleotide libraries (modified SELEX), are the conventional methods used to generate nuclease-resistant aptamers. 14–18 Macugen, an approved aptamer drug, is a vivid example of nuclease-resistant aptamers generated with modified SELEX. 19 However, modified nucleotides must be compatible with polymerases in SELEX, and such postselection modifications can affect aptamer specificity and affinity.…”

Next‐Generation Nucleic Acid Aptamers with Two‐Base‐Modified Nucleotides Have Improved Binding Affinity and Potency

“…Aptamers are single‐stranded oligonucleotides (RNA or DNA) that can bind to their targets with high affinities and specificities because of their ability to adopt different three‐dimensional shapes in solution . Aptamers can be developed in a standard molecular biology laboratory and against a wide range of targets including small molecules, peptides and whole cells.…”

“…Small size, low immunogenicity and thermostability make aptamers a promising tool for diagnostic and clinical applications. Traditionally, aptamers have been developed by SELEX (systematic evolution of ligands by exponential enrichment), a reiterative process involving selection by incubating target molecules with an oligonucleotide library and enrichment of the selected oligonucleotides by amplification . One drawback of current aptamer selection approach is the lack of diversity in the nucleic acid library with only four nucleobase compositions.…”

Aptamer and aptamer pharmaceuticals

“…16 [40] , 基本满足了筛选 核酸(HNA)). 2′-氨基修饰是最早应用的修饰种类 [42] , 但由于其对核糖构象的不利影响 [43] , 这种修饰方案目 前已很少使用. 2′-F修饰具有较强的抗降解能力, 对核 糖空间构象的影响也比较小, 在SELEX技术中得到了 广泛的应用 [44] .…”