<scp>d</scp>-/<scp>l</scp>-Isothymidine incorporation in the core sequence of aptamer BC15 enhanced its binding affinity to the hnRNP A1 protein

Li, Liyu; Yang, Xiantao; Li, Kunfeng; Guangpu, Zhang; Ma, Yuan; Cai, Baobin; Li, Shaohua; Ding, Hongmei; Deng, Jiali; Nan, Xiyan; Sun, Jing; Wu, Yun; Shao, Ningsheng; Zhang, Lihe; Yang, Zhenjun

doi:10.1039/c8ob01454j

Cited by 6 publications

(3 citation statements)

References 54 publications

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“…Modifications of the sugar ring can improve nuclease stability and prolong serum half-life. Similarly, the 2'-OH positions of RNA aptamers can be substituted with 2'-F 82 , 83 , 84 , 2'-OMe 85 , 2'-NH 2 , 2'-LNA 86 , 87 , and 2'-d-/l-isonucleoside 88 , 89 . Substitution of non-natural nucleotides into oligonucleotides is achieved by mutating T7 RNA polymerase.…”

Section: Rna Modificationmentioning

confidence: 99%

Emerging Progress of RNA-Based Antitumor Therapeutics

Fu¹,

Dong²,

Wu³

et al. 2023

Int. J. Biol. Sci.

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RNA-based therapeutics (e.g., mRNAs, siRNAs, microRNAs, ASOs, and saRNAs) have considerable potential for tumor treatment. The development and optimization of RNA modifications and delivery systems enable the stable and efficient delivery of RNA cargos in vivo to elicit an antitumor response. Targeted RNA-based therapeutics with multiple specificities and high efficacies are now available. In this review, we discuss progress in RNA-based antitumor therapeutics, including mRNAs, siRNAs, miRNAs, ASOs, saRNAs, RNA aptamers, and CRISPR-based gene editing. We focus on the immunogenicity, stability, translation efficiency, and delivery of RNA drugs, and summarize their optimization and the development of delivery systems. In addition, we describe the mechanisms by which RNA-based therapeutics induce antitumor responses. Furthermore, we review the merits and limitations of RNA cargos and their therapeutic potential for cancers.

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Section: Rna Modificationmentioning

confidence: 99%

Emerging Progress of RNA-Based Antitumor Therapeutics

Fu¹,

Dong²,

Wu³

et al. 2023

Int. J. Biol. Sci.

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“…Circular dichroism (CiD) [71], nuclear magnetic resonance (NMR) [72], X-ray crystallography [73] as well as molecular modeling [74] are useful to probe aptamer-target interactions. Using the structural information, the full-length aptamer can be subjected to post-SELEX to obtain the optimal sequence [75][76][77][78][79][80].…”

Section: Experimental Design Of Selexmentioning

confidence: 99%

A Bottom-Up Approach for Developing Aptasensors for Abused Drugs: Biosensors in Forensics

et al. 2019

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Aptamer-based point-of-care (POC) diagnostics platforms may be of substantial benefit in forensic analysis as they provide rapid, sensitive, user-friendly, and selective analysis tools for detection. Aptasensors have not yet been adapted commercially. However, the significance of the applications of aptasensors in the literature exceeded their potential. Herein, in this review, a bottom-up approach is followed to describe the aptasensor development and application procedure, starting from the synthesis of the corresponding aptamer sequence for the selected analyte to creating a smart surface for the sensitive detection of the molecule of interest. Optical and electrochemical biosensing platforms, which are designed with aptamers as recognition molecules, detecting abused drugs are critically reviewed, and existing and possible applications of different designs are discussed. Several potential disciplines in which aptamer-based biosensing technology can be of greatest value, including forensic drug analysis and biological evidence, are then highlighted to encourage researchers to focus on developing aptasensors in these specific areas.

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“…BC15 (74 nt) is a DNA aptamer that was found by tissue slide-based SELEX, which has a high affinity to hnRNP A1 and A2/B1 ( Li et al, 2009 ), showing better antiproliferation activity in the HepG2 cell line ( Ku et al, 2015 ). We found that the core sequence of BC15, BC15-31 (31 nt), showed higher target affinity and further enhanced bioactivity and stability with isothymidine (isoT) modification at 5′- and 3′-terminal regions ( Li et al, 2018 ). Application of neutral cytidinyl lipid DNCA, through H-binding and π-π interaction, to reduce or avoid the use of cystine-based cationic lipid CLD ( Ma et al, 2016 ), gave a safe and effective delivery system for oligonucleotides ( Ma et al, 2018 , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Selective Anti-melanoma Effect of Phosphothioated Aptamer Encapsulated by Neutral Cytidinyl/Cationic Lipids

Wang

et al. 2021

Front. Cell Dev. Biol.

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BC15-31 is a DNA aptamer that targets heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), which plays a crucial role in the process of pre-RNA maturation and is also essential for the rapid proliferation of tumor cells. In this research, we modified BC15-31 with a phosphorothioate (PS) backbone, LNA, and 2-O-MOE to enhance its stability and target affinity. In addition, a neutral cytidinyl lipid (DNCA) and a cationic lipid (CLD) were mixed to encapsulate modified aptamers with the aim of improving their cell permeability with low toxicity. Under the DNCA/CLD package, aptamers are mainly distributed in the nucleus. A modified sequence WW-24 showed an excellent selective anti-melanoma (A375 cells, ∼25 nM, 80%) activity, targeted to both hnRNP A1 and hnRNP A2/B1 found by the BLI experiment, and induced more early and late apoptosis in vitro, which also showed stronger antitumor effect and longer accumulation time in vivo. These results provide a new strategy for further clinical applications.

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d-/l-Isothymidine incorporation in the core sequence of aptamer BC15 enhanced its binding affinity to the hnRNP A1 protein

Abstract: Truncation of BC15 and d-/l-isothymidine modification of its core sequence greatly enhanced the binding affinity and selectivity to the hnRNP A1 protein.

Cited by 6 publications

References 54 publications

Emerging Progress of RNA-Based Antitumor Therapeutics

Emerging Progress of RNA-Based Antitumor Therapeutics

A Bottom-Up Approach for Developing Aptasensors for Abused Drugs: Biosensors in Forensics

Selective Anti-melanoma Effect of Phosphothioated Aptamer Encapsulated by Neutral Cytidinyl/Cationic Lipids

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