Oligonucleotide Aptamers: New Tools for Targeted Cancer Therapy

Abstract

Aptamers are a class of small nucleic acid ligands that are composed of RNA or single-stranded DNA oligonucleotides and have high specificity and affinity for their targets. Similar to antibodies, aptamers interact with their targets by recognizing a specific three-dimensional structure and are thus termed “chemical antibodies.” In contrast to protein antibodies, aptamers offer unique chemical and biological characteristics based on their oligonucleotide properties. Hence, they are more suitable for the development of novel clinical applications. Aptamer technology has been widely investigated in various biomedical fields for biomarker discovery, in vitro diagnosis, in vivo imaging, and targeted therapy. This review will discuss the potential applications of aptamer technology as a new tool for targeted cancer therapy with emphasis on the development of aptamers that are able to specifically target cell surface biomarkers. Additionally, we will describe several approaches for the use of aptamers in targeted therapeutics, including aptamer-drug conjugation, aptamer-nanoparticle conjugation, aptamer-mediated targeted gene therapy, aptamer-mediated immunotherapy, and aptamer-mediated biotherapy.

A self-assembling RNA aptamer-based graphene oxide sensor for the turn-on detection of theophylline in serum

“…Standard 2′ OH RNA molecules are unstable in biological fluids and have a half-life of less than 1 min in serum (de Smidt et al, 1991). Several different methods have been developed to improve RNA stability in biological fluids, mostly relying on substitutions of the 2′ OH functional group on RNA with 2′ fluoro, 2′ amino, or 2′ O-methoxy motifs and/or replacement of the phosphodiester backbone with boranophosphate or phosphorothioate moieties (Sun et al, 2014). However, these modifications may result in structural changes to the RNA sequence, thereby affecting the binding affinity, and would greatly increase the cost of potential applications (De-los-Santos-Álvarez et al, 2007).…”

A unique aptamer-drug conjugate for targeted therapy of multiple myeloma

“…Our findings also indicate the clinical potential of ApDCs, which not only selectively inhibit MM tumors, but also have little or no off-target side effect in patients. To initiate clinical trials, further improvements and additional preclinical testing may be needed as discussed previously (12). Interestingly, this ApDC technology can be used as a universal platform to treat many cancers by simply replacing the aptamer sequence with one that targets different tumor biomarkers.…”

A self-assembling RNA aptamer-based nanoparticle sensor for fluorometric detection of Neomycin B in milk

“…However, most (70 %) reported aptamers are composed of RNA [6]. Based on existing evidence, the presence of a 2′-OH group and non-Watson-Crick base pairing allow RNA aptamers to fold into more diverse 3D structures than DNA [7]. Many small molecules interact with RNA better than with DNA [8].…”

“…Substitutions of the 2′-OH functional group on RNA with 2′-fluoro, 2′-amino, or 2′-O-methoxy motifs, and/or replacements of the phosphodiester backbone with boranophosphate or phosphorothioate moieties are the most common modifications aimed at increasing nuclease resistance [7]. Other effective modifications have been based on locked nucleic acid technology [9] or Bmirror^RNA sequence structures [10].…”