Laboratory evolution of artificially expanded DNA gives redesignable aptamers that target the toxic form of anthrax protective antigen

Biondi, Elisa; Lane, Joshua D.; Das, Debasis; DasGupta, Saurja; Piccirilli, Joseph A.; Hoshika, Shuichi; Bradley, Kevin M.; Krantz, Bryan A.; Benner, Steven A.

doi:10.1093/nar/gkw890

Cited by 47 publications

(54 citation statements)

References 35 publications

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“…CD-spectroscopy experiments revealed an unknown peak that does not correspond to those normally seen for G-quadruplexes. This finding might indicate a completely new folding behaviour of aptamers containing an expanded genetic alphhabet, which is comparable to what has been shown for SOMAmers (see Section 'Aptamers with modified nucleobases') [49 ]. Further structural studies will be elemental to elucidate this.…”

Section: Aptamers With An Extended Genetic Alphabetsupporting

confidence: 73%

“…The affinity of the resultant AEGIS-aptamer, which contained two dPs, could be improved to 35 nM by shortening of the aptamer and strengthening of a stem with two more dP-dZ instead of dG-dC pairs, which implies that dP-dZ is more stable in a duplex than dG-dC [49 ]. Because of G-rich regions, the authors suspected the AEGIS-aptamer to fold into a G-quadruplex structure.…”

Section: Aptamers With An Extended Genetic Alphabetmentioning

confidence: 99%

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Customised nucleic acid libraries for enhanced aptamer selection and performance

Pfeiffer

Rosenthal

Siegl

et al. 2017

Current Opinion in Biotechnology

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Section: Aptamers With An Extended Genetic Alphabetsupporting

confidence: 73%

Section: Aptamers With An Extended Genetic Alphabetmentioning

confidence: 99%

Customised nucleic acid libraries for enhanced aptamer selection and performance

Pfeiffer

Rosenthal

Siegl

et al. 2017

Current Opinion in Biotechnology

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“…A laboratory in vitro evolution (LIVE) experiment based on an artificially expanded genetic information system (AEGIS) was reported by Biondi et al An AEGIS aptamer that binds to an isolated protein target was outlined against an antigen from Bacillus anthracis. The AEGIS aptamer showed improved stability and binding of the aptamer to its target [154].…”

Section: Spiegelmersmentioning

confidence: 99%

Aptamers Chemistry: Chemical Modifications and Conjugation Strategies

et al. 2019

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Soon after they were first described in 1990, aptamers were largely recognized as a new class of biological ligands that can rival antibodies in various analytical, diagnostic, and therapeutic applications. Aptamers are short single-stranded RNA or DNA oligonucleotides capable of folding into complex 3D structures, enabling them to bind to a large variety of targets ranging from small ions to an entire organism. Their high binding specificity and affinity make them comparable to antibodies, but they are superior regarding a longer shelf life, simple production and chemical modification, in addition to low toxicity and immunogenicity. In the past three decades, aptamers have been used in a plethora of therapeutics and drug delivery systems that involve innovative delivery mechanisms and carrying various types of drug cargos. However, the successful translation of aptamer research from bench to bedside has been challenged by several limitations that slow down the realization of promising aptamer applications as therapeutics at the clinical level. The main limitations include the susceptibility to degradation by nucleases, fast renal clearance, low thermal stability, and the limited functional group diversity. The solution to overcome such limitations lies in the chemistry of aptamers. The current review will focus on the recent arts of aptamer chemistry that have been evolved to refine the pharmacological properties of aptamers. Moreover, this review will analyze the advantages and disadvantages of such chemical modifications and how they impact the pharmacological properties of aptamers. Finally, this review will summarize the conjugation strategies of aptamers to nanocarriers for developing targeted drug delivery systems. Molecules 2020, 25, 3 2 of 51 molecules [2]. Nowadays, the aptamer field covers various biomedical applications, including [3], therapeutic [4-6], aptasensors [7], biosensors [8,9], diagnostic [10,11], and imaging systems [12].Aptamers need to be stabilized for in vivo use against nuclease degradation, and their small size makes them susceptible to renal filtration. Aptamers' stabilization can be attained by chemically modifying them using different approaches. Moreover, introducing chemical modifications into nucleic acid libraries increases the interaction capabilities of aptamers and thereby their target spectrum [12]. Modified aptamers may show improved chemical diversity relative to aptamers composed entirely of natural DNA or RNA nucleotides and expand their applications in diagnostics, therapeutics, and nanotechnology [1].Chemical modifications of aptamer oligonucleotides are needed mainly to enhance their resistance to nuclease degradation and lowering their renal filtration. Additionally, chemical modifications, in some cases, may increase the aptamer-binding affinity [13]. Many approaches have been introduced to promote the stability of aptamers without altering their binding affinity and specificity against their targets. These approaches include chemical modification of the phosphate...

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“…This paradigm shift has enabled the synthesis of longer oligomers and in vitro evolution; applications such as XNA aptamers (Biondi et al, 2016;Ferreira-Bravo et al, 2015;Kimoto, Yamashige, Matsunaga, Yokoyama, & Hirao, 2013;Yang, Chen, Chamberlin, & Benner, 2010;Yu et al, 2012), nucleic acid enzymes (Hollenstein, Hipolito, Lam, & Perrin, 2009;Taylor et al, 2014), and nanostructures (Taylor et al, 2016) are now well established. XNAs have gone from chemically synthesized short oligomers suitable for biophysical characterization and sequence-defined applications (e.g., antisense) to enzymatically synthesized synthetic genetic materials.…”

Section: Background Informationmentioning

confidence: 99%

XNA Synthesis and Reverse Transcription by Engineered Thermophilic Polymerases

Cozens

Pinheiro

2018

CP Chemical Biology

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The B-family polymerases of hyperthermophilic archaea have proven an exceptional platform for engineering polymerases with extended substrate spectra, despite multiple mechanisms for detecting and avoiding incorporation of non-cognate substrates. These polymerases can efficiently synthesize and reverse-transcribe a number of xenonucleic acids (XNAs) that differ significantly from the canonical B-form of DNA. We present here a protocol for hexitol nucleic acid (HNA) synthesis by an engineered Thermococcus gorgonarius polymerase variant, including adaptation for large-scale synthesis and purification, and for other XNAs. We describe XNA purification and reverse transcription (with a previously reported XNA RT also based on Thermococcus gorgonarius), as well as key considerations for the characterization and optimization of XNA reactions. © 2018 by John Wiley & Sons, Inc.

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Laboratory evolution of artificially expanded DNA gives redesignable aptamers that target the toxic form of anthrax protective antigen

Cited by 47 publications

References 35 publications

Customised nucleic acid libraries for enhanced aptamer selection and performance

Customised nucleic acid libraries for enhanced aptamer selection and performance

Aptamers Chemistry: Chemical Modifications and Conjugation Strategies

XNA Synthesis and Reverse Transcription by Engineered Thermophilic Polymerases

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