Therapeutic Applications of DNA and RNA Aptamers

Thiel, Kristina W.; Giangrande, Paloma H.

doi:10.1089/oli.2009.0199

Cited by 151 publications

(131 citation statements)

References 114 publications

(160 reference statements)

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“…After gating on singlet alive CD11b þ cells (Fig. 3B) The anti-IL4Ra aptamer restrains 4T1 tumor progression, promote CD8 þ T-cell infiltration, and reduces the number of MDSCs infiltrating the tumor Aptamers not only can bind their ligands but may also trigger a biologic function (21). Thus, we investigated whether chronic administration of anti-IL4Ra aptamer may influence tumor growth.…”

Section: Resultsmentioning

confidence: 99%

Aptamer-Mediated Blockade of IL4Rα Triggers Apoptosis of MDSCs and Limits Tumor Progression

et al. 2012

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In addition to promoting tumor progression and metastasis by enhancing angiogenesis and invasion, myeloidderived suppressor cells (MDSC) and tumor-associated macrophage (TAM) also inhibit antitumor T-cell functions and limit the efficacy of immunotherapeutic interventions. Despite the importance of these leukocyte populations, a simple method for their specific depletion has not been developed. In this study, we generated an RNA aptamer that blocks the murine or human IL-4 receptor-a (IL4Ra or CD124) that is critical for MDSC suppression function. In tumor-bearing mice, this anti-IL4Ra aptamer preferentially targeted MDSCs and TAM and unexpectedly promoted their elimination, an effect that was associated with an increased number of tumorinfiltrating T cells and a reduction in tumor growth. Mechanistic investigations of aptamer-triggered apoptosis in MDSCs confirmed the importance of IL4Ra-STAT6 pathway activation in MDSC survival. Our findings define a straightforward strategy to deplete MDSCs and TAMs in vivo, and they strengthen the concept that IL4Ra signaling is pivotal for MDSC survival. More broadly, these findings suggest therapeutic strategies based on IL4Ra signaling blockades to arrest an important cellular mechanism of tumoral immune escape mediated by MDSCs and TAM in cancer. Cancer Res; 72(6); 1373-83. Ó2012 AACR.

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Section: Resultsmentioning

confidence: 99%

Aptamer-Mediated Blockade of IL4Rα Triggers Apoptosis of MDSCs and Limits Tumor Progression

et al. 2012

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“…Starting with a library containing random RNA sequences with ~10 (34-36) varieties of RNA molecules, in vitro binding, elution and reverse polymerase chain reaction (PCR) amplification techniques allow for the selection of RNA molecules that efficiently bind to a specific receptor or ligand with high affinity (37,38). Conceptually, the marked specificity and high affinity of aptamers to a wide variety of targets, coupled with the ease of design and molecular engineering, as mentioned above, have made them broadly popular and highly suitable for development as clinical diagnostic and therapeutic agents in cancer research (39)(40)(41). Pegaptanib (Pfizer̸Eyetech), an aptamer targeting VEGF, has already been approved by the FDA for clinical use in treating AMD (42).…”

Section: Aptamers and Selexmentioning

confidence: 99%

Clinical applications of nucleic acid aptamers in cancer

Pei

Zhang

Liu

2014

Molecular and Clinical Oncology

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Abstract. Nucleic acid aptamers are small single-stranded DNA or RNA oligonucleotide segments, which bind to their targets with high affinity and specificity via unique three-dimensional structures. Aptamers are generated by an iterative in vitro selection process, termed as systematic evolution of ligands by exponential enrichment. Owing to their specificity, non-immunogenicity, non-toxicity, easily modified chemical structure and wide range of targets, aptamers appear to be ideal candidates for various clinical applications (diagnosis or treatment), such as cell detection, target diagnosis, molecular imaging and drug delivery. Several aptamers have entered the clinical pipeline for applications in diseases such as macular degeneration, coronary artery bypass graft surgery and various types of cancer. The aim of this review was to summarize and highlight the clinical applications of aptamers in cancer diagnosis and treatment.

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“…The later discovery by Andrew Fire and Craig Mello, regarding the ability of RNA to selectively control gene expression in animals through the process of RNA interference (RNAi) [57], has cemented the place of RNA as an extremely important molecule for study with far reaching applications in medicine, science, and engineering. In particular, the capacity to understand and The first class represents RNA based functionalities with desirable chemical or biological activity including ribozymes [82,83], aptamers [84][85][86], riboswitches [87,88], and RNAi inducing agents (e.g. short interfering RNA (siRNA), micro RNA (miRNA), etc) [89,92] as well as functionalities with a the three-dimensional structure of the RNA.…”

Section: Introductionmentioning

confidence: 99%

Engineered RNA Nanodesigns for Applications in RNA Nanotechnology

Afonin¹,

Lindsay²,

Shapiro³

2013

DNA and RNA Nanotechnology

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IntroductionThe physical world presents a very different landscape at the nanometer scale. Physical phenomena such as inertia and gravity vanish from view; instead the interactions of matter and energy are dominated by other phenomena like wave-particle duality, uncertainty, and quantum electrodynamics. Nanotechnology is the engineering of functional systems at this scale, where the axioms that govern material and device design differ dramatically from those found at the macroscale level. More precisely, "nanotechnology" typically encompasses both the miniaturization of existing technologies to the nanoscale, and the discipline of engineering molecular-scale systems from the bottom up, producing constructs with fundamentally new qualities that revolutionize human engineering, from materials and manufacturing, electronics, and information technology, to medicine, biotechnology, energy, and even security. The array of goals and applications in nanotechnology intersects with an equally wide array of techniques and materials with their own emergent properties in the field. One such branch is concerned with the re-engineering of biological mechanisms, systems, and molecules in new forms with new utilities, broadly termed bio-nanotechnology.The field of nanotechnology taking advantage of nucleic acids has its origins in the work of Nadrian Seeman and coworkers who have, over the past 30 years, spearheaded the development of DNA nano-object fabrication utilizing DNA self-assembly [1][2][3][4][5][6]. Briefly, DNA nanotechnology uses the nature of DNA complementarity for the construction of DNA tiles with discrete secondary structure by canonical WatsonCrick interactions (G-C and A-T base pairing), using a relatively small number of structural rules fundamentally based on Holliday junction motifs. The use of these rules has resulted in the engineering and characterization of numerous DNA 3D nanoscaffolds with different connectiviities [7][8][9][10][11][12][13][14][15][16][17][18] and the ability for some of them to promote targeted delivery by functioning as DNA nano-capsules [19][20][21] or DNA nano-carriers for other functionialities [22]. Another powerful technique called DNA "origami", developed by Paul Rothemund [23], has been extended from its original scope for designing different 2D DNA shapes [24] and functional templates [25][26][27][28] Abstract Nucleic acids have emerged as an extremely promising platform for nanotechnological applications because of their unique biochemical properties and functions. RNA, in particular, is characterized by relatively high thermal stability, diverse structural flexibility, and its capacity to perform a variety of functions in nature. These properties make RNA a valuable platform for bio-nanotechnology, specifically RNA Nanotechnology, that can create de novo nanostructures with unique functionalities through the design, integration, and re-engineering of powerful mechanisms based on a variety of existing RNA structures and their fundamental biochemical properties. This review...

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Therapeutic Applications of DNA and RNA Aptamers

Cited by 151 publications

References 114 publications

Aptamer-Mediated Blockade of IL4Rα Triggers Apoptosis of MDSCs and Limits Tumor Progression

Aptamer-Mediated Blockade of IL4Rα Triggers Apoptosis of MDSCs and Limits Tumor Progression

Clinical applications of nucleic acid aptamers in cancer

Engineered RNA Nanodesigns for Applications in RNA Nanotechnology

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