Improved Anti-Prion Nucleic Acid Aptamers by Incorporation of Chemical Modifications

2020 ◽  
Vol 30 (6) ◽  
pp. 414-421 ◽  
Author(s):  
Jussara Amato ◽  
Tsukasa Mashima ◽  
Yuji O. Kamatari ◽  
Kazuo Kuwata ◽  
Ettore Novellino ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Chemical Modifications ◽  
Nucleic Acid Aptamers

scholarly journals Artificial Specific Binders Directly Recovered from Chemically Modified Nucleic Acid Libraries

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Yuuya Kasahara ◽  
Masayasu Kuwahara
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Biological Research ◽  
Future Research ◽  
Chemical Modifications ◽  
Additional Time ◽  
Nucleotide Analogs ◽  
Enzymatic Production ◽  
Chemically Modified ◽  
Nucleic Acid Aptamers

Specific binders comprised of nucleic acids, that is, RNA/DNA aptamers, are attractive functional biopolymers owing to their potential broad application in medicine, food hygiene, environmental analysis, and biological research. Despite the large number of reports on selection of natural DNA/RNA aptamers, there are not many examples of direct screening of chemically modified nucleic acid aptamers. This is because of (i) the inferior efficiency and accuracy of polymerase reactions involving transcription/reverse-transcription of modified nucleotides compared with those of natural nucleotides, (ii) technical difficulties and additional time and effort required when using modified nucleic acid libraries, and (iii) ambiguous efficacies of chemical modifications in binding properties until recently; in contrast, the effects of chemical modifications on biostability are well studied using various nucleotide analogs. Although reports on the direct screening of a modified nucleic acid library remain in the minority, chemical modifications would be essential when further functional expansion of nucleic acid aptamers, in particular for medical and biological uses, is considered. This paper focuses on enzymatic production of chemically modified nucleic acids and their application to random screenings. In addition, recent advances and possible future research are also described.

scholarly journals Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes

2017 ◽  
Vol 18 (8) ◽  
pp. 1683 ◽  
Author(s):  
Shuaijian Ni ◽  
Houzong Yao ◽  
Lili Wang ◽  
Jun Lu ◽  
Feng Jiang ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Chemical Modifications ◽  
Nucleic Acid Aptamers

Nucleic Acid Aptamers as Novel Class of Therapeutics to Mitigate Alzheimer’s Disease Pathology

2013 ◽  
Vol 10 (4) ◽  
pp. 442-448 ◽  
Author(s):  
Rudi K. Tannenberg ◽  
Hadi Al. Shamaileh ◽  
Lasse H. Lauridsen ◽  
Jagat R. Kanwar ◽  
Peter R. Dodd ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nucleic Acid ◽  
Nucleic Acid Aptamers

scholarly journals Chemical conjugation of nucleic acid aptamers and synthetic polymers

2021 ◽  
Author(s):  
Maria Nerantzaki ◽  
Capucine Loth ◽  
Jean-Francois Lutz
Keyword(s):  
Nucleic Acid ◽  
Synthetic Polymers ◽  
Specific Sequence ◽  
Biological Targets ◽  
Nucleic Acid Aptamers ◽  
Chemical Conjugation ◽  
Sequence Dependent

Nucleic acid aptamers are chemically-synthesized single-stranded oligonucleotides that fold into specific sequence-dependent configurations. Due to their exceptional recognition properties towards a variety of biological targets, they find applications in many...

scholarly journals Hybrid-Type SELEX for the Selection of Artificial Nucleic Acid Aptamers Exhibiting Cell Internalization Activity

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 888
Author(s):  
Hiro Uemachi ◽  
Yuuya Kasahara ◽  
Keisuke Tanaka ◽  
Takumi Okuda ◽  
Yoshihiro Yoneda ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Surface Protein ◽  
Functional Screening ◽  
Nucleic Acid Aptamers ◽  
Hybrid Type ◽  
Cell Internalization ◽  
Promising Target ◽  
A Cell ◽  
Exponential Enrichment

Nucleic acid aptamers have attracted considerable attention as next-generation pharmaceutical agents and delivery vehicles for small molecule drugs and therapeutic oligonucleotides. Chemical modification is an effective approach for improving the functionality of aptamers. However, the process of selecting appropriately modified aptamers is laborious because of many possible modification patterns. Here, we describe a hybrid-type systematic evolution of ligands by exponential enrichment (SELEX) approach for the generation of the artificial nucleic acid aptamers effective against human TROP2, a cell surface protein identified by drug discovery as a promising target for cancer therapy. Capillary electrophoresis SELEX was used for the pre-screening of multiple modified nucleic acid libraries and enrichment of TROP2 binding aptamers in the first step, followed by functional screening using cell-SELEX in the second step for the generation of cell-internalizing aptamers. One representative aptamer, Tac-B1, had a nanomolar-level affinity to human TROP2 and exhibited elevated capacity for internalization by cells. Because of the growing interest in the application of aptamers for drug delivery, our hybrid selection approach has great potential for the generation of functional artificial nucleic acid aptamers with ideal modification patterns in vitro.

scholarly journals Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

2021 ◽  
Vol 17 ◽  
pp. 622-629
Author(s):  
Naohiro Horie ◽  
Takao Yamaguchi ◽  
Shinji Kumagai ◽  
Satoshi Obika
Keyword(s):  
Nucleic Acid ◽  
Binding Affinity ◽  
Antisense Oligonucleotides ◽  
Modified Oligonucleotides ◽  
Biophysical Properties ◽  
Chemical Modifications ◽  
Antisense Technology ◽  
Strong Affinity ◽  
The Stability

Chemical modifications have been extensively used for therapeutic oligonucleotides because they strongly enhance the stability against nucleases, binding affinity to the targets, and efficacy. We previously reported that oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing the thymine (T) nucleobase show excellent biophysical properties for applications in antisense technology. In this paper, we describe the synthesis of GuNA[Me] phosphoramidites bearing other typical nucleobases including adenine (A), guanine (G), and 5-methylcytosine (mC). The phosphoramidites were successfully incorporated into oligonucleotides following the method previously developed for the GuNA[Me]-T-modified oligonucleotides. The binding affinity of the oligonucleotides modified with GuNA[Me]-A, -G, or -mC toward the complementary single-stranded DNAs or RNAs was systematically evaluated. All of the GuNA[Me]-modified oligonucleotides were found to have a strong affinity for RNAs. These data indicate that GuNA[Me] could be a useful modification for therapeutic antisense oligonucleotides.

scholarly journals Molecular Imaging with Nucleic Acid Aptamers

2011 ◽  
Vol 18 (27) ◽  
pp. 4195-4205 ◽  
Author(s):  
H. Hong ◽  
S. Goel ◽  
Y. Zhang ◽  
W. Cai
Keyword(s):  
Nucleic Acid ◽  
Molecular Imaging ◽  
Nucleic Acid Aptamers
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