Lipophilic 2′-O-Acetal Ester RNAs: Synthesis, Thermal Duplex Stability, Nuclease Resistance, Cellular Uptake, and siRNA Activity after Spontaneous Naked Delivery

ChemBioChem ◽  
2016 ◽  
Vol 17 (21) ◽  
pp. 2054-2062 ◽  
Author(s):  
Annabelle Biscans ◽  
Jean-Rémi Bertrand ◽  
Josephine Dubois ◽  
Jacqueline Rüger ◽  
Jean-Jacques Vasseur ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Duplex Stability ◽  
Nuclease Resistance

4′-C-Trifluoromethyl modified oligodeoxynucleotides: synthesis, biochemical studies, and cellular uptake properties

2019 ◽  
Vol 17 (22) ◽  
pp. 5550-5560 ◽  
Author(s):  
Yifei Zhou ◽  
Chuanlong Zang ◽  
Huawei Wang ◽  
Jiajun Li ◽  
Zenghui Cui ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Cell Permeability ◽  
Biochemical Studies ◽  
Nuclease Resistance

Introducing a 4′-C-trifluoromethyl (4′-CF3) modification into oligodeoxynucleotides (ODNs) leads to improved nuclease resistance and increased cell permeability.

scholarly journals Shaping Rolling Circle Amplification Products into DNA Nanoparticles by Incorporation of Modified Nucleotides and Their Application to In Vitro and In Vivo Delivery of a Photosensitizer

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1833 ◽  
Author(s):  
Kyoung-Ran Kim ◽  
Pascal Röthlisberger ◽  
Seong Kang ◽  
Kihwan Nam ◽  
Sangyoup Lee ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cellular Uptake ◽  
Rolling Circle Amplification ◽  
Modified Nucleotides ◽  
Rolling Circle ◽  
Dna Nanoparticles ◽  
Nuclease Resistance ◽  
Cellular Uptake Efficiency

Rolling circle amplification (RCA) is a robust way to generate DNA constructs, which are promising materials for biomedical applications including drug delivery because of their high biocompatibility. To be employed as a drug delivery platform, however, the DNA materials produced by RCA need to be shaped into nanoparticles that display both high cellular uptake efficiency and nuclease resistance. Here, we showed that the DNA nanoparticles (DNPs) can be prepared with RCA and modified nucleotides that have side-chains appended on the nucleobase are capable of interacting with the DNA strands of the resulting RCA products. The incorporation of the modified nucleotides improved cellular uptake efficiency and nuclease resistance of the DNPs. We also demonstrated that these DNPs could be employed as carriers for the delivery of a photosensitizer into cancer cells to achieve photodynamic therapy upon irradiation at both the in vitro and in vivo levels.

Triazole- and Tetrazole-Bridged Nucleic Acids: Synthesis, Duplex Stability, Nuclease Resistance, and in Vitro and in Vivo Antisense Potency

2016 ◽  
Vol 82 (1) ◽  
pp. 12-24 ◽  
Author(s):  
Yasunori Mitsuoka ◽  
Tsuyoshi Yamamoto ◽  
Akira Kugimiya ◽  
Reiko Waki ◽  
Fumito Wada ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Duplex Stability ◽  
Nuclease Resistance

Synthesis, binding, nuclease resistance and cellular uptake properties of 2′- O -acetalester-modified oligonucleotides containing cationic groups

2015 ◽  
Vol 23 (17) ◽  
pp. 5360-5368 ◽  
Author(s):  
Annabelle Biscans ◽  
Sonia Rouanet ◽  
Jean-Rémi Bertrand ◽  
Jean-Jacques Vasseur ◽  
Christelle Dupouy ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Modified Oligonucleotides ◽  
Nuclease Resistance

scholarly journals A critical analysis of methods used to investigate the cellular uptake and subcellular localization of RNA therapeutics

2020 ◽  
Vol 48 (14) ◽  
pp. 7623-7639 ◽  
Author(s):  
Kirsten Deprey ◽  
Nefeli Batistatou ◽  
Joshua A Kritzer
Keyword(s):  
Cellular Uptake ◽  
Critical Analysis ◽  
Genetic Diseases ◽  
Specific Protein ◽  
Cell Penetration ◽  
Chemical Modifications ◽  
Aberrant Splicing ◽  
Promising Strategy ◽  
Nuclease Resistance ◽  
Delivery Strategies

Abstract RNA therapeutics are a promising strategy to treat genetic diseases caused by the overexpression or aberrant splicing of a specific protein. The field has seen major strides in the clinical efficacy of this class of molecules, largely due to chemical modifications and delivery strategies that improve nuclease resistance and enhance cell penetration. However, a major obstacle in the development of RNA therapeutics continues to be the imprecise, difficult, and often problematic nature of most methods used to measure cell penetration. Here, we review these methods and clearly distinguish between those that measure total cellular uptake of RNA therapeutics, which includes both productive and non-productive uptake, and those that measure cytosolic/nuclear penetration, which represents only productive uptake. We critically analyze the benefits and drawbacks of each method. Finally, we use key examples to illustrate how, despite rigorous experimentation and proper controls, our understanding of the mechanism of gymnotic uptake of RNA therapeutics remains limited by the methods commonly used to analyze RNA delivery.

Modification of oligonucleotides with weak basic residues via the 2′-O-carbamoylethyl linker for improving nuclease resistance without loss of duplex stability and antisense activity

2019 ◽  
Vol 17 (19) ◽  
pp. 4835-4842
Author(s):  
Yoshiaki Masaki ◽  
Keishi Yamamoto ◽  
Keita Yoshida ◽  
Atsuya Maruyama ◽  
Takahito Tomori ◽  
...  
Keyword(s):  
Duplex Stability ◽  
Nuclease Resistance

For the improvement of nuclease resistance, four kinds of new modifications through a carbamoylethyl linker were designed.

scholarly journals Oligonucleotides containing a piperazino-modified 2′-amino-LNA monomer exhibit very high duplex stability and remarkable nuclease resistance

2015 ◽  
Vol 51 (19) ◽  
pp. 4024-4027 ◽  
Author(s):  
Chenguang Lou ◽  
Birte Vester ◽  
Jesper Wengel
Keyword(s):  
Complementary Dna ◽  
Dna And Rna ◽  
Duplex Stability ◽  
Nuclease Resistance ◽  
Exonucleolytic Degradation ◽  
Very High

Incorporation of a novel piperazino-modified 2′-amino-LNA monomer (PipLNA-T) into oligonucleotides leads to a pronounced affinity increase against complementary DNA and RNA and a strong stabilising effect against 3′-exonucleolytic degradation.

Amido-Bridged Nucleic Acids (AmNAs): Synthesis, Duplex Stability, Nuclease Resistance, and in Vitro Antisense Potency

ChemBioChem ◽  
2012 ◽  
Vol 13 (17) ◽  
pp. 2513-2516 ◽  
Author(s):  
Aiko Yahara ◽  
Ajaya Ram Shrestha ◽  
Tsuyoshi Yamamoto ◽  
Yoshiyuki Hari ◽  
Takashi Osawa ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Duplex Stability ◽  
Nuclease Resistance
Sign in / Sign up

Export Citation Format

Share Document