Recent Advances in SELEX Technology and Aptamer Applications in Biomedicine

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Abstract

Aptamers are short DNA/RNA oligonucleotides capable of binding to target molecules with high affinity and specificity. The process of selecting an aptamer is called Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Thanks to the inherit merits, aptamers have been used in a wide range of applications, including disease diagnosis, targeted delivery agents and therapeutic uses. To date, great achievements regarding the selection, modifications and application of aptamers have been made. However, few aptamer-based products have already successfully entered into clinical and industrial use. Besides, it is still a challenge to obtain aptamers with high affinity in a more efficient way. Thus, it is important to comprehensively review the current shortage and achievement of aptamer-related technology. In this review, we first present the limitations and notable advances of aptamer selection. Then, we compare the different methods used in the kinetic characterization of aptamers. We also discuss the impetus and developments of the clinical application of aptamers.

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Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase.

L Gold, C Tuerk (1990)

High-affinity nucleic acid ligands for a protein were isolated by a procedure that depends on alternate cycles of ligand selection from pools of variant sequences and amplification of the bound species. Multiple rounds exponentially enrich the population for the highest affinity species that can be clonally isolated and characterized. In particular one eight-base region of an RNA that interacts with the T4 DNA polymerase was chosen and randomized. Two different sequences were selected by this procedure from the calculated pool of 65,536 species. One is the wild-type sequence found in the bacteriophage mRNA; one is varied from wild type at four positions. The binding constants of these two RNA's to T4 DNA polymerase are equivalent. These protocols with minimal modification can yield high-affinity ligands for any protein that binds nucleic acids as part of its function; high-affinity ligands could conceivably be developed for any target molecule.

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Aptamers as therapeutics

Anthony Keefe, Supriya Pai, Andrew Ellington (2010)

Key Points Aptamers are single-stranded oligonucleotides that fold into defined architectures and bind to targets such as proteins. In binding proteins they often inhibit protein–protein interactions and thereby may elicit therapeutic effects such as antagonism. Aptamers are discovered using SELEX (systematic evolution of ligands by exponential enrichment), a directed in vitro evolution technique in which large libraries of degenerate oligonucleotides are iteratively and alternately partitioned for target binding. They are then amplified enzymatically until functional sequences are identified by the sequencing of cloned individuals. For most therapeutic purposes, aptamers are truncated to reduce synthesis costs, modified at the sugars and capped at their termini to increase nuclease resistance, and conjugated to polyethylene glycol or another entity to reduce renal filtration rates. The first aptamer approved for a therapeutic application was pegaptanib sodium (Macugen; Pfizer/Eyetech), which was approved in 2004 by the US Food and Drug Administration for macular degeneration. Eight other aptamers are currently undergoing clinical evaluation for various haematology, oncology, ocular and inflammatory indications. Aptamers are ultimately chemically synthesized in a readily scalable process in which specific conjugation points are introduced with defined stereochemistry. Unlike some protein therapeutics, aptamers do not elicit antibodies, and because aptamers generally contain sugars modified at their 2′-positions, Toll-like receptor-mediated innate immune responses are also abrogated. As aptamers are oligonucleotides they can be readily assembled into supramolecular multi-component structures using hybridization. Owing to the fact that binding to appropriate cell-surface targets can lead to internalization, aptamers can also be used to deliver therapeutic cargoes such as small interfering RNA. Supramolecular assemblies of aptamers and delivery agents have already been demonstrated in vivo and may pave the way for further therapeutic strategies with this modality in the future.

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Aptamers as targeted therapeutics: current potential and challenges

Jiehua Zhou, John M. Rossi (2016)

Nucleic acid aptamers offer several advantages over traditional antibodies, but their clinical translation has been delayed by several factors, including insufficient potency, lack of safety data and high production costs. Here, Zhou and Rossi provide an overview of aptamer generation, focusing on recent technological advances and clinical development, as well as challenges and lessons learned.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 14 October 2017

Publication date Collection: October 2017

Volume: 18

Issue: 10

Electronic Location Identifier: 2142

Affiliations

[1 ]School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China; zhenjianzhuo@ 123456163.com (Z.Z.); lijie_bio@ 123456126.com (J.L.); maxzhangzk@ 123456cuhk.edu.hk (Z.Z.)

[2 ]Law Sau Fai Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China; yu.yy01@ 123456hotmail.com (Y.Y.); wangml1240@ 123456163.com (M.W.); liujin_hkbu@ 123456163.com (J.L.); wxho0606@ 123456163.com (X.W.)

[3 ]Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China

[4 ]Institute of Precision Medicine and Innovative Drug Discovery, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China

[5 ]Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518000, China

Author notes

[* ]Correspondence: aipinglu@ 123456hkbu.edu.hk (A.L.); zhangge@ 123456hkbu.edu.hk (G.Z.); zhangbaoting@ 123456cuhk.edu.hk (B.Z.); Tel.: +852-3411-2456 (A.L.); +852-3411-2958 (G.Z.); +852-39434285 (B.Z.)

[†]

These authors contributed equally to this work.

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Ge Zhang https://orcid.org/0000-0002-7807-7695

Article

Publisher ID: ijms-18-02142

DOI: 10.3390/ijms18102142

PMC ID: 5666824

PubMed ID: 29036890

SO-VID: 409fd830-4ca4-47e9-b36a-96b6430b9786

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Recent Advances in SELEX Technology and Aptamer Applications in Biomedicine

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Entomologia Generalis

Most cited references 105

Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase.

Aptamers as therapeutics

Aptamers as targeted therapeutics: current potential and challenges

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