title: Post-SELEX optimization of aptamers.
abstract: Aptamers are functional single-stranded DNA or RNA oligonucleotides, selected in vitro by SELEX (Systematic Evolution of Ligands by Exponential Enrichment), which can fold into stable unique three-dimensional structures that bind their target ligands with high affinity and specificity. Although aptamers show a number of favorable advantages such as better stability and easier modification when compared with the properties of antibodies, only a handful of aptamers have entered clinical trials and only one, pegaptanib, has received US Food and Drug Administration approval for clinical use. The main reasons that limit the practical application of aptamers are insufficient nuclease stability, bioavailability, thermal stability, or even affinity. Some aptamers obtained from modified libraries show better properties; however, polymerase amplification of nucleic acids containing non-natural bases is currently a primary drawback of the SELEX process. This review focuses on several post-SELEX optimization strategies of aptamers identified in recent years. We describe four common methods in detail: truncation, chemical modification, bivalent or multivalent aptamer construction, and mutagenesis. We believe that these optimization strategies should improve one or more specific properties of aptamers, and the type of feature(s) selected for improvement will be dependent on the application purpose.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Shunxiang
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Second Military Medical University, Shanghai, 200433, China. bhjiao@smmu.edu.cn.|Marine Biopharmaceutical Institute, College of Marine Military Medicine, Second Military Medical University, Shanghai, 200433, China. bhjiao@smmu.edu.cn.
authors.forename: Binghua
authors.initials: B
authors.lastname: Jiao
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Second Military Medical University, Shanghai, 200433, China. lhwang@smmu.edu.cn.
authors.forename: Lianghua
authors.initials: L
authors.lastname: Wang
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D017277:Drug Approval / Q000331:legislation & jurisprudence; D052156:SELEX Aptamer Technique / Q000379:methods*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D052157:Aptamers, Nucleotide
keywords: Aptamer; Chemical modification; Mutation; Optimization; Polyvalent ligand; Truncation