Grafting multi-maleimides on antisense oligonucleotide to enhance its cellular uptake and gene silencing capability

2020 ◽  
Vol 56 (54) ◽  
pp. 7439-7442
Author(s):  
Yuanyuan Guo ◽  
Jiao Zhang ◽  
Gaifang Pan ◽  
Chung Hang Jonathan Choi ◽  
Ping Wang ◽  
...  

Grafting multi-maleimides on antisense oligonucleotide enables its click conjugation to membrane proteins, inducing promoted non-endocytic cell internalization and gene knockdown.

2014 ◽  
Vol 473 (1-2) ◽  
pp. 579-590 ◽  
Author(s):  
Diana Guzman-Villanueva ◽  
Ibrahim M. El-Sherbiny ◽  
Alexander V. Vlassov ◽  
Dea Herrera-Ruiz ◽  
Hugh D.C. Smyth

2014 ◽  
Vol 185 ◽  
pp. 109-120 ◽  
Author(s):  
Eliz Amar-Lewis ◽  
Aharon Azagury ◽  
Ramesh Chintakunta ◽  
Riki Goldbart ◽  
Tamar Traitel ◽  
...  

2017 ◽  
Vol 5 (44) ◽  
pp. 8799-8813 ◽  
Author(s):  
B. Dumontel ◽  
M. Canta ◽  
H. Engelke ◽  
A. Chiodoni ◽  
L. Racca ◽  
...  

The surface chemistry and charge of zinc oxide nanocrystals influence their behaviour in biological fluids. A novel lipid bilayer assembly is developed to shield ZnO nanocrystals improving their stability and cell internalization.


2018 ◽  
pp. S267-S279 ◽  
Author(s):  
E. BÖHMOVÁ ◽  
D. MACHOVÁ ◽  
M. PECHAR ◽  
R. POLA ◽  
K. VENCLÍKOVÁ ◽  
...  

Cell-penetrating compounds are substances that enhance the cellular uptake of various molecular cargoes that do not easily cross the cellular membrane. The majority of cell-penetrating compounds described in the literature are cell-penetrating peptides (CPPs). This review summarizes the various structural types of cell-penetrating compounds, with the main focus on CPPs. The authors present a brief overview of the history of CPPs, discuss the various types of conjugation of CPPs to biologically active cargoes intended for cell internalization, examine the cell-entry mechanisms of CPPs, and report on the applications of CPPs in research and in preclinical and clinical studies.


2010 ◽  
Vol 141 (3) ◽  
pp. 339-346 ◽  
Author(s):  
Seung-Young Lee ◽  
Myung Sook Huh ◽  
Seulki Lee ◽  
So Jin Lee ◽  
Hyunjin Chung ◽  
...  

2015 ◽  
Vol 43 (19) ◽  
pp. 9350-9361 ◽  
Author(s):  
Daniela Castanotto ◽  
Min Lin ◽  
Claudia Kowolik ◽  
LiAnn Wang ◽  
Xiao-Qin Ren ◽  
...  

2010 ◽  
Vol 24 (3-4) ◽  
pp. 303-307 ◽  
Author(s):  
Petr Praus ◽  
Eva Kocišová ◽  
Peter Mojzeš ◽  
Josef Štepánek ◽  
Franck Sureau ◽  
...  

Time-resolved confocal microspectrofluorometry and fluorescence microimaging were used to monitor how the model antisense oligonucleotide is transported into 3T3 living cells and distributed inside them. Phosphorothioate analog of 15-mer oligothymidylate labeled by ATTO 425 was complexed with Zn(II) 5,10,15,20-tetrakis(4-N-methylpyridyl) porphyrin as an uptake-mediating agent. Homodyne phase-resolved technique based on a high frequency analog modulation of both exciting diode laser and detector image intensifier was used for time-resolved measurements. Decay-time data obtained within a broad range spectral region have provided unique information about the fate of both fluorophores inside the cell.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yeong Chae Ryu ◽  
Kyung Ah Kim ◽  
Byoung Choul Kim ◽  
Hui-Min David Wang ◽  
Byeong Hee Hwang

Abstract Background Gene silencing using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine. Results Among the novel fusion peptides and siRNAs, nanocomplexes have enhanced cellular uptake and gene silencing effect in vitro and improved retention and gene silencing effects of siRNAs in vivo. Oligoarginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased retention time of siRNAs at the site of the tumor. Finally, nanocomplexes demonstrated significant in vivo gene silencing effect without overt tissue damage and immune cell infiltration. Conclusions The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene silencing.


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