scholarly journals Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole)

2015 ◽  
Vol 11 ◽  
pp. 493-498 ◽  
Author(s):  
Friederike Danneberg ◽  
Alice Ghidini ◽  
Plamena Dogandzhiyski ◽  
Elisabeth Kalden ◽  
Roger Strömberg ◽  
...  
Keyword(s):  
Antisense Oligonucleotides ◽  
Peptide Nucleic Acids ◽  
Substrate Recognition ◽  
Rna Degradation ◽  
Rna Cleavage ◽  
Site Specific ◽  
Substrate Specificities ◽  
Dna Conjugates ◽  
Aggregation Phenomena ◽  
Effective Site

Tris(2-aminobenzimidazole) conjugates with antisense oligonucleotides are effective site-specific RNA cleavers. Their mechanism of action is independent of metal ions. Here we investigate conjugates with peptide nucleic acids (PNA). RNA degradation occurs with similar rates and substrate specificities as in experiments with DNA conjugates we performed earlier. Although aggregation phenomena are observed in some cases, proper substrate recognition is not compromised. While our previous synthesis of 2-aminobenzimidazoles required an HgO induced cyclization step, a mercury free variant is described herein.

Azobenzene-modified antisense oligonucleotides for site-specific cleavage of RNA with photocontrollable property

RSC Advances ◽  
2016 ◽  
Vol 6 (96) ◽  
pp. 93398-93402 ◽  
Author(s):  
Xingyu Wang ◽  
Xingguo Liang
Keyword(s):  
Antisense Oligonucleotides ◽  
Rnase H ◽  
Rna Cleavage ◽  
Site Specific

Photoresponsive azobenzene-modified antisense oligonucleotides for site-specific RNA cleavage by RNase H.

scholarly journals RNase H1-Dependent Antisense Oligonucleotides Are Robustly Active in Directing RNA Cleavage in Both the Cytoplasm and the Nucleus

2017 ◽  
Vol 25 (9) ◽  
pp. 2075-2092 ◽  
Author(s):  
Xue-Hai Liang ◽  
Hong Sun ◽  
Joshua G. Nichols ◽  
Stanley T. Crooke
Keyword(s):  
Antisense Oligonucleotides ◽  
Rna Cleavage

scholarly journals Antisense Oligonucleotides Containing an Internal, Non-Nucleotide-Based Linker Promote Site-Specific Cleavage of RNA

1996 ◽  
Vol 24 (4) ◽  
pp. 760-765 ◽  
Author(s):  
M. A. Reynolds ◽  
T. A. Beck ◽  
P. B. Say ◽  
D. A. Schwartz ◽  
B. P. Dwyer ◽  
...  
Keyword(s):  
Antisense Oligonucleotides ◽  
Site Specific

Development of cholate conjugated hybrid polymeric micelles for FXR receptor mediated effective site-specific delivery of paclitaxel

2018 ◽  
Vol 42 (20) ◽  
pp. 17021-17032 ◽  
Author(s):  
Sivaraj Mehnath ◽  
Mukherjee Arjama ◽  
Mariappan Rajan ◽  
Murugaraj Jeyaraj
Keyword(s):  
Cholic Acid ◽  
Tumor Targeting ◽  
Polymeric Micelles ◽  
Polymeric Micelle ◽  
Site Specific ◽  
Effective Delivery ◽  
Effective Site ◽  
Micelle System

The aim of the present study was to explore the tumor targeting potential of a cholic acid (CA) conjugated polymeric micelle system for the effective delivery of paclitaxel (PTX).

pH responsive doxorubucin loaded zein nanoparticle crosslinked pectin hydrogel as effective site-specific anticancer substrates

2020 ◽  
Vol 152 ◽  
pp. 1027-1037 ◽  
Author(s):  
Priyanka Kaushik ◽  
Eepsita Priyadarshini ◽  
Kamla Rawat ◽  
Paulraj Rajamani ◽  
H.B. Bohidar
Keyword(s):  
Ph Responsive ◽  
Site Specific ◽  
Effective Site

scholarly journals Understanding the effect of controlling phosphorothioate chirality in the DNA gap on the potency and safety of gapmer antisense oligonucleotides

2020 ◽  
Vol 48 (4) ◽  
pp. 1691-1700 ◽  
Author(s):  
Michael E Østergaard ◽  
Cheryl L De Hoyos ◽  
W Brad Wan ◽  
Wen Shen ◽  
Audrey Low ◽  
...  
Keyword(s):  
Antisense Oligonucleotides ◽  
Therapeutic Index ◽  
Rna Cleavage ◽  
Systematic Analysis ◽  
Phosphodiester Backbone ◽  
High Affinity ◽  
Backbone Modification ◽  
Therapeutic Profile ◽  
In Cells

Abstract Therapeutic oligonucleotides are often modified using the phosphorothioate (PS) backbone modification which enhances stability from nuclease mediated degradation. However, substituting oxygen in the phosphodiester backbone with sulfur introduce chirality into the backbone such that a full PS 16-mer oligonucleotide is comprised of 215 distinct stereoisomers. As a result, the role of PS chirality on the performance of antisense oligonucleotides (ASOs) has been a subject of debate for over two decades. We carried out a systematic analysis to determine if controlling PS chirality in the DNA gap region can enhance the potency and safety of gapmer ASOs modified with high-affinity constrained Ethyl (cEt) nucleotides in the flanks. As part of this effort, we examined the effect of systematically controlling PS chirality on RNase H1 cleavage patterns, protein mislocalization phenotypes, activity and toxicity in cells and in mice. We found that while controlling PS chirality can dramatically modulate interactions with RNase H1 as evidenced by changes in RNA cleavage patterns, these were insufficient to improve the overall therapeutic profile. We also found that controlling PS chirality of only two PS linkages in the DNA gap was sufficient to modulate RNase H1 cleavage patterns and combining these designs with simple modifications such as 2′-OMe to the DNA gap resulted in dramatic improvements in therapeutic index. However, we were unable to demonstrate improved potency relative to the stereorandom parent ASO or improved safety over the 2′-OMe gap-modified stereorandom parent ASO. Overall, our work shows that while controlling PS chirality can modulate RNase H1 cleavage patterns, ASO sequence and design are the primary drivers which determine the pharmacological and toxicological properties of gapmer ASOs.

scholarly journals Two-terpyridine {middle dot} Cu(II) complexes-containing antisense systems for rapid and highly site-specific RNA cleavage

2000 ◽  
Vol 44 (1) ◽  
pp. 279-280 ◽  
Author(s):  
H. Inoue ◽  
T. Furukawa ◽  
T. Tamura ◽  
Y. Komatsu ◽  
E. Ohtsuka
Keyword(s):  
Rna Cleavage ◽  
Site Specific
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