Strategies to manipulate the performance of aptamers in SELEX, post-SELEX and microenvironment

Aptamers are short single-stranded DNA or RNA oligonucleotides isolated from randomized libraries, presenting high affinity and specificity toward targets with similar to antibodies. Recently, aptamers have demonstrated their outstanding application potential ranging from biosensors, bioimaging, and therapeutics due to various advantages including low immunogenicity, ease of large-scale synthesis, low batch-to-batch variation, easily chemical modification, and programmability. However, the current overall success rate of aptamer is far from being satisfactory, and still needs to overwhelm the major obstacle in affinity, specificity, and stability for practical application. The efficient strategy of manipulating the binding performance of aptamers, and improving their performance in practical application is of great significance. Herein, we review the challenges and advances in manipulating the binding performance (e.g., affinity, specificity, and stability) of aptamers to obtain high-quality aptamers by comprehensive analyzing their structure and properties. This mainly includes interfering with the SELEX protocol to obtain excellent parental aptamers, engineering aptamers in post-SELEX process and matching the optimal working microenvironment. Moreover, the perspectives of future direction are also summarized. We hope to provide researchers with alternative strategies for enhancing the performance of aptamers in practical applications and promoting the explosive development of aptamers in related fields.