Current Advances in Aptamers for Cancer Diagnosis and Therapy

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Nucleic acid aptamers are single-stranded oligonucleotides that interact with target molecules with high affinity and specificity in unique three-dimensional structures. Aptamers are generally isolated by a simple selection process called systematic evolution of ligands by exponential enrichment (SELEX) and then can be chemically synthesized and modified. Because of their high affinity and specificity, aptamers are promising agents for biomarker discovery, as well as cancer diagnosis and therapy. In this review, we present recent progress and challenges in aptamer and SELEX technology and highlight some representative applications of aptamers in cancer therapy.

Related collections

Most cited references 191

Record: found
Abstract: found
Article: not found

The blockade of immune checkpoints in cancer immunotherapy.

Drew M Pardoll (2012)

Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.

0 comments Cited 5128 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

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.

0 comments Cited 959 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

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.

0 comments Cited 588 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Cancers (Basel)

Journal ID (iso-abbrev): Cancers (Basel)

Journal ID (publisher-id): cancers

Title: Cancers

Publisher: MDPI

ISSN (Electronic): 2072-6694

Publication date (Electronic): 03 January 2018

Publication date Collection: January 2018

Volume: 10

Issue: 1

Electronic Location Identifier: 9

Affiliations

[1 ]Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd, Duarte, CA 91010, USA; shori@ 123456coh.org (S.-i.H.); albherrera@ 123456coh.org (A.H.)

[2 ]Drug Discovery & Disease Research Laboratory, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan

[3 ]Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd, Duarte, CA 91010, USA

Author notes

[* ]Correspondence: jrossi@ 123456coh.org (J.J.R.); jzhou@ 123456coh.org (J.Z.)

[†]

The first two authors contributed equally to this work.

Author information

Jiehua Zhou https://orcid.org/0000-0002-2088-1218

Article

Publisher ID: cancers-10-00009

DOI: 10.3390/cancers10010009

PMC ID: 5789359

PubMed ID: 29301363

SO-VID: 663a4ba4-e6c5-4687-af5a-a6a6ffcf53e5

License:

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/).

Current Advances in Aptamers for Cancer Diagnosis and Therapy

Read this article at

Abstract

Related collections

Negative Pressure Wound Therapy

Most cited references 191

The blockade of immune checkpoints in cancer immunotherapy.

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

Aptamers as therapeutics

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Categories

Comments

Comment on this article

Similar content 615

Cited by 49

Most referenced authors 3,587