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Review
. 2017 Jan 6:57:61-79.
doi: 10.1146/annurev-pharmtox-010716-104558.

Aptamers as Therapeutics

Shahid M Nimjee  1 , Rebekah R White  2 , Richard C Becker  3 , Bruce A Sullenger  2   4
Affiliations
Review

Aptamers as Therapeutics

Shahid M Nimjee et al. Annu Rev Pharmacol Toxicol. .

Abstract

Aptamers are single-stranded nucleic acid molecules that bind to and inhibit proteins and are commonly produced by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers undergo extensive pharmacological revision, which alters affinity, specificity, and therapeutic half-life, tailoring each drug for a specific clinical need. The first therapeutic aptamer was described 25 years ago. Thus far, one aptamer has been approved for clinical use, and numerous others are in preclinical or clinical development. This review presents a short history of aptamers and SELEX, describes their pharmacological development and optimization, and reviews potential treatment of diseases including visual disorders, thrombosis, and cancer.

Keywords: SELEX; antidote; aptamer; pharmacology; therapeutics.

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Figures

Figure 1
Figure 1
The TAR aptamer serves as a decoy, preventing the Tat protein from binding the endogenous TAR RNA, thereby inhibiting HIV gene expression and replication. Modified with permission from the Annual Review of Medicine. Abbreviations: HIV, human immunodeficiency virus; RNA, ribonucleic acid; TAR, trans-activation response.
Figure 2
Figure 2
Systematic evolution of ligands by exponential enrichment (SELEX). Modified with permission from the Annual Review of Medicine.
Figure 3
Figure 3
Toggle SELEX, whereby the pool is toggled between orthologs of the target protein to select an aptamer that binds to both targets. This facilitates preclinical evaluation of the aptamer. Modified with permission from the Annual Review of Medicine.
Figure 4
Figure 4
Antidote oligonucleotide control of aptamer activity. By binding to the aptamer using Watson-Crick base pairing, the aptamer cannot form its three-dimensional structure, thereby preventing it from binding to its target. Modified with permission from the Annual Review of Medicine.
See this image and copyright information in PMC

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