From selection hits to clinical leads: progress in aptamer discovery

Maier, Keith E.; Levy, Matthew

doi:10.1038/mtm.2016.14

Cited by 83 publications

(71 citation statements)

References 86 publications

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“…For the most part, progress in the solid phase nucleic acid synthesis field has not changed this fundamental approach. For R&D purposes, shortened aptamers with 20 to 50 nucleotides in length can be generated in individual labs using "lab scale" DNA or RNA synthesizers [39] (e.g., Expedite 8909, ABI394).…”

Section: Synthesis Of Dna Aptamersmentioning

confidence: 99%

Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes

Yao

Wang

et al. 2017

IJMS

245

181

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Nucleic acid aptamers have minimal immunogenicity, high chemical synthesis production, low cost and high chemical stability when compared with antibodies. However, the susceptibility to nuclease degradation, rapid excretion through renal filtration and insufficient binding affinity hindered their development as drug candidates for therapeutic applications. In this review, we will discuss methods to conquer these challenges and highlight recent developments of chemical modifications and technological advances that may enable early aptamers to be translated into clinical therapeutics.

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Section: Synthesis Of Dna Aptamersmentioning

confidence: 99%

Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes

Yao

Wang

et al. 2017

IJMS

245

181

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“…This structural complexity results in a high probability of selecting an aptamer that can strongly and specifically interact with the target of interest through hydrogen bonds, salt bridges, van der Waals, hydrophobic and/or electrostatic interactions. The high affinity and selectivity for the target, as well as the multiplicity of possible target types, make aptamers a valid alternative to antibodies in a wide variety of applications, from therapeutics (as drugs or drug-delivery systems) to diagnostic and sensing devices [8][9][10][11][12][13][14][15]. Nucleic acid aptamers exhibit significant advantages over antibodies, such as smaller size, lower immunogenicity, remarkable stability in a wide range of pH (≈4-9) and temperature; in addition, aptamers the chemical and enzymatic stability of aptamers, but can also contribute to greatly broaden their chemical diversity, improving their binding affinity and specificity for a selected target.…”

Section: Description and Selection Of Nucleic Acid Aptamersmentioning

confidence: 99%

“…Nevertheless, new aptamer-based candidate (Adapted from ref [38]. by permission of The Royal Society of Chemistry) drugs are undertaking clinical trials [9,32], and this gives us hope that increasingly more aptamers and aptamer-like compounds will be approved as drugs in the next future.…”

Section: Description and Selection Of Nucleic Acid Aptamersmentioning

confidence: 99%

G-quadruplex-based aptamers against protein targets in therapy and diagnostics

Platella

Riccardi

Montesarchio

et al. 2017

Biochimica et Biophysica Acta (BBA) - General Subjects

136

116

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Nucleic acid aptamers are single-stranded DNA or RNA molecules identified to recognize with high affinity specific targets including proteins, small molecules, ions, whole cells and even entire organisms, such as viruses or bacteria. They can be identified from combinatorial libraries of DNA or RNA oligonucleotides by SELEX technology, an in vitro iterative selection procedure consisting of binding (capture), partitioning and amplification steps. Remarkably, many of the aptamers selected against biologically relevant protein targets are G-rich sequences that can fold into stable G-quadruplex (G4) structures. Aiming at disseminating novel inspiring ideas within the scientific community in the field of G4-structures, the emphasis of this review is placed on: 1) recent advancements in SELEX technology for the efficient and rapid identification of new candidate aptamers (introduction of microfluidic systems and next generation sequencing); 2) recurrence of G4 structures in aptamers selected by SELEX against biologically relevant protein targets; 3) discovery of several G4-forming motifs in important regulatory regions of the human or viral genome bound by endogenous proteins, which per se can result into potential aptamers; 4) an updated overview of G4-based aptamers with therapeutic potential and 5) a discussion on the most attractive G4-based aptamers for diagnostic applications. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

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“…Similar to protein antibodies, aptamers specifically recognize their targets, which can include nucleic acids, proteins, cells, and even tissue, with high affinity . Aptamers are considered “chemical antibodies,” given that they are chemically synthesized and have the ability to specifically bind their targets through 3D recognition . To target lymphoma in particular, CD30‐specific aptamers have been previously developed and clinically validated …”

Section: Introductionmentioning

confidence: 99%

Aptamer‐Engineered Natural Killer Cells for Cell‐Specific Adaptive Immunotherapy

Yang

Wen

et al. 2019

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Natural killer (NK) cells are a key component of the innate immune system as they can attack cancer cells without prior sensitization. However, due to lack of cell‐specific receptors, NK cells are not innately able to perform targeted cancer immunotherapy. Aptamers are short single‐stranded oligonucleotides that specifically recognize their targets with high affinity in a similar manner to antibodies. To render NK cells with target‐specificity, synthetic CD30‐specific aptamers are anchored on cell surfaces to produce aptamer‐engineered NK cells (ApEn‐NK) without genetic alteration or cell damage. Under surface‐anchored aptamer guidance, ApEn‐NK specifically bind to CD30‐expressing lymphoma cells but do not react to off‐target cells. The resulting specific cell binding of ApEn‐NK triggers higher apoptosis/death rates of lymphoma cells compared to parental NK cells. Additionally, experiments with primary human NK cells demonstrate the potential of ApEn‐NK to specifically target and kill lymphoma cells, thus presenting a potential new approach for targeted immunotherapy by NK cells.

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From selection hits to clinical leads: progress in aptamer discovery

Cited by 83 publications

References 86 publications

Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes

Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes

G-quadruplex-based aptamers against protein targets in therapy and diagnostics

Aptamer‐Engineered Natural Killer Cells for Cell‐Specific Adaptive Immunotherapy

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