An <scp>l</scp>‐RNA Aptamer with Expanded Chemical Functionality that Inhibits MicroRNA Biogenesis

Kabza, Adam M.; Sczepanski, Jonathan T.

doi:10.1002/cbic.201700362

Cited by 28 publications

(20 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The efficient mirror-image transcription system may enable enzymatic preparation of L-RNA molecules to further enable clinical applications of nuclease-resistant aptamer biosensors and drugs 16 or studies on mirror-image or cross-chiral ribozymes and aptamers. [21][22][23] The enzymatically transcribed L-5S rRNA shown in this study could be used as one component in a future effort to assemble a mirror-image ribosome, a step toward the realization of mirrorimage life. 4 The development of a mirror-image reverse transcription system serves as an important amendment to the mirror-image central dogma of molecular biology, with both conceptual and practical significance to the mirror-image biology field.…”

Section: Discussionmentioning

confidence: 99%

Mirror-Image Gene Transcription and Reverse Transcription

Wei

Jiang

Liu

et al. 2019

Chem

View full text Add to dashboard Cite

Toward building a chirally inverted version of the central dogma of molecular biology, Zhu and colleagues realized the transcription of a mirror-image gene into L-RNA and reverse transcription into L-DNA by synthetic D-polymerases. They enzymatically transcribed full-length mirror-image 5S rRNA and demonstrated a comprehensive mirror-image transcription, reverse transcription, PCR, and sequencing toolbox.

show abstract

Section: Discussionmentioning

confidence: 99%

Mirror-Image Gene Transcription and Reverse Transcription

Wei

Jiang

Liu

et al. 2019

Chem

View full text Add to dashboard Cite

show abstract

“…Spiegelmers also undergo similar different strategies and chemical modifications as natural aptamers to enhance their stability against nucleases and improve their binding affinity [143]. A nuclease-resistant modified l-RNA aptamer (MLRA) with cationic nucleotide, 5 aminoallyl-uridine, was isolated in an in vitro selection process and this spiegelmer was capable of binding oncogenic pre-miR-19a with exceptional affinity, and the cationic modification was absolutely crucial for binding [150]. An L-RNA aptamer targeting the HIV-1 trans-activation responsive (TAR) RNA was developed.…”

Section: Spiegelmersmentioning

confidence: 99%

Aptamers Chemistry: Chemical Modifications and Conjugation Strategies

et al. 2019

View full text Add to dashboard Cite

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...

show abstract

“…Despite these limitations, allyl-amino-UTP (U aa TP) was used in an in vitro selection experiment aimed at raising an anti-ATP aptamer [ 252 ]. More recently, Kabza and Sczepanski used the same U aa TP to isolate an aptamer against the oncogenic precursor microRNA 19a (pre-miR-19a) which was converted to its Spiegelmer via solid-phase synthesis using the L-U aa -phosphoramidite [ 253 ]. The resulting L-RNA aptamer bound its target with a slightly lower affinity than its D-counterpart ( K d values of 2.2 and 0.72 nM, respectively) but efficiently inhibited the Dicer-mediated processing of the miR target (IC 50 ≅ 4 nM) in vitro.…”

Section: Recent Chemical Modifications Of Aptamersmentioning

confidence: 99%

Nucleic Acid Aptamers: Emerging Applications in Medical Imaging, Nanotechnology, Neurosciences, and Drug Delivery

Röthlisberger

Gasse

Hollenstein

2017

IJMS

View full text Add to dashboard Cite

Recent progresses in organic chemistry and molecular biology have allowed the emergence of numerous new applications of nucleic acids that markedly deviate from their natural functions. Particularly, DNA and RNA molecules—coined aptamers—can be brought to bind to specific targets with high affinity and selectivity. While aptamers are mainly applied as biosensors, diagnostic agents, tools in proteomics and biotechnology, and as targeted therapeutics, these chemical antibodies slowly begin to be used in other fields. Herein, we review recent progress on the use of aptamers in the construction of smart DNA origami objects and MRI and PET imaging agents. We also describe advances in the use of aptamers in the field of neurosciences (with a particular emphasis on the treatment of neurodegenerative diseases) and as drug delivery systems. Lastly, the use of chemical modifications, modified nucleoside triphosphate particularly, to enhance the binding and stability of aptamers is highlighted.

show abstract

An l‐RNA Aptamer with Expanded Chemical Functionality that Inhibits MicroRNA Biogenesis

Cited by 28 publications

References 31 publications

Mirror-Image Gene Transcription and Reverse Transcription

Mirror-Image Gene Transcription and Reverse Transcription

Aptamers Chemistry: Chemical Modifications and Conjugation Strategies

Nucleic Acid Aptamers: Emerging Applications in Medical Imaging, Nanotechnology, Neurosciences, and Drug Delivery

Contact Info

Product

Resources

About