Recent progress of SELEX methods for screening nucleic acid aptamers

Nucleic acid aptamers are oligonucleotide sequences screened by an in vitro methodology called Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Known as "chemical antibodies", aptamers can achieve specific recognition towards the targets through conformational changes with high affinity, and possess multiple attractive features including, but not limited to, easy and inexpensive to prepare by chemical synthesis, relatively stable and low batch-to-batch variability, easy modification and signal amplification, and low immunogenicity. Now, aptamers are attracting researchers' attentions from more than 25 disciplines, and have showed great potential for application and economic benefits in disease diagnosis, environmental detection, food security, drug delivery and discovery. Although some aptamers exist naturally as the ligand-binding elements of riboswitches, SELEX is a recognized method for aptamers screening. After thirty-two years of development, a series of SELEX methods have been investigated and developed, as well as have shown unique advantages to improve sequence performances or to explore screening mechanisms. This review would mainly focus on the novel or improved SELEX methods that are available in the past five years. Firstly, we present a clear overview of the aptamer's history, features, and SELEX development. Then, we highlight the specific examples to emphasize the recent progress of SELEX methods in terms of carrier materials, technical improvements, real sample-improved screening, post-SELEX and other methods, as well as their respects of screening strategies, implementation features, screening parameters. Finally, we discuss the remaining challenges that have the potential to hinder the success of SELEX and aptamers in practical applications, and provide the suggestions and future directions for developing more convenient, efficient, and stable SELEX methods in the future.