A one-pot modular assembly strategy for triple-play enhanced cytosolic siRNA delivery

2019 ◽  
Vol 7 (3) ◽  
pp. 901-913 ◽  
Author(s):  
Daping Xie ◽  
Junjie Du ◽  
Moxyel Bao ◽  
Anwei Zhou ◽  
Chunli Tian ◽  
...  

Robust efficiency for cytosolic small interfering RNA (siRNA) delivery is of great importance for effective gene therapy.

RSC Advances ◽  
2020 ◽  
Vol 10 (73) ◽  
pp. 45059-45066
Author(s):  
Huan Peng ◽  
Weihong Ji ◽  
Ruichen Zhao ◽  
Zhiguo Lu ◽  
Jun Yang ◽  
...  

pH-sensitive zwitterionic polycarboxybetaine could complex siRNA in an acidic environment and could be used as a non-viral vector for safe siRNA delivery.


2018 ◽  
Vol 115 (12) ◽  
pp. E2696-E2705 ◽  
Author(s):  
Jiahe Li ◽  
Connie Wu ◽  
Wade Wang ◽  
Yanpu He ◽  
Elad Elkayam ◽  
...  

Small interfering RNA (siRNA) represents a promising class of inhibitors in both fundamental research and the clinic. Numerous delivery vehicles have been developed to facilitate siRNA delivery. Nevertheless, achieving highly potent RNA interference (RNAi) toward clinical translation requires efficient formation of RNA-induced gene-silencing complex (RISC) in the cytoplasm. Here we coencapsulate siRNA and the central RNAi effector protein Argonaute 2 (Ago2) via different delivery carriers as a platform to augment RNAi. The physical clustering between siRNA and Ago2 is found to be indispensable for enhanced RNAi. Moreover, by utilizing polyamines bearing the same backbone but distinct cationic side-group arrangements of ethylene diamine repeats as the delivery vehicles, we find that the molecular structure of these polyamines modulates the degree of siRNA/Ago2-mediated improvement of RNAi. We apply this strategy to silence the oncogene STAT3 and significantly prolong survival in mice challenged with melanoma. Our findings suggest a paradigm for RNAi via the synergistic coassembly of RNA with helper proteins.


Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2570 ◽  
Author(s):  
Inés Serrano-Sevilla ◽  
Álvaro Artiga ◽  
Scott G. Mitchell ◽  
Laura De Matteis ◽  
Jesús M. de la Fuente

Natural polysaccharides are frequently used in the design of drug delivery systems due to their biocompatibility, biodegradability, and low toxicity. Moreover, they are diverse in structure, size, and charge, and their chemical functional groups can be easily modified to match the needs of the final application and mode of administration. This review focuses on polysaccharidic nanocarriers based on chitosan and hyaluronic acid for small interfering RNA (siRNA) delivery, which are highly positively and negatively charged, respectively. The key properties, strengths, and drawbacks of each polysaccharide are discussed. In addition, their use as efficient nanodelivery systems for gene silencing applications is put into context using the most recent examples from the literature. The latest advances in this field illustrate effectively how chitosan and hyaluronic acid can be modified or associated with other molecules in order to overcome their limitations to produce optimized siRNA delivery systems with promising in vitro and in vivo results.


Nanoscale ◽  
2018 ◽  
Vol 10 (23) ◽  
pp. 10952-10962 ◽  
Author(s):  
Marco A. Deriu ◽  
Nicolas Tsapis ◽  
Magali Noiray ◽  
Gianvito Grasso ◽  
Nabil El Brahmi ◽  
...  

In the field of dendrimers targeting small interfering RNA (siRNA) delivery, dendrimer structural properties, such as the surface chemistry, play a crucial role in the efficiency of complexation.


2019 ◽  
Vol 33 (12) ◽  
pp. 14129-14136 ◽  
Author(s):  
Bolin Wu ◽  
Haitao Shang ◽  
Xitian Liang ◽  
Yixin Sun ◽  
Hui Jing ◽  
...  

2020 ◽  
Vol 6 (30) ◽  
pp. eaba5379 ◽  
Author(s):  
Md. Nazir Hossen ◽  
Lin Wang ◽  
Harisha R. Chinthalapally ◽  
Joe D. Robertson ◽  
Kar-Ming Fung ◽  
...  

Gene silencing using small-interfering RNA (siRNA) is a viable therapeutic approach; however, the lack of effective delivery systems limits its clinical translation. Herein, we doped conventional siRNA-liposomal formulations with gold nanoparticles to create “auroliposomes,” which significantly enhanced gene silencing. We targeted MICU1, a novel glycolytic switch in ovarian cancer, and delivered MICU1-siRNA using three delivery systems—commercial transfection agents, conventional liposomes, and auroliposomes. Low-dose siRNA via transfection or conventional liposomes was ineffective for MICU1 silencing; however, in auroliposomes, the same dose gave >85% gene silencing. Efficacy was evident from both in vitro growth assays of ovarian cancer cells and in vivo tumor growth in human ovarian cell line—and patient-derived xenograft models. Incorporation of gold nanoparticles shifted intracellular uptake pathways such that liposomes avoided degradation within lysosomes. Auroliposomes were nontoxic to vital organs. Therefore, auroliposomes represent a novel siRNA delivery system with superior efficacy for multiple therapeutic applications.


2021 ◽  
Vol 16 (12) ◽  
pp. 2534
Author(s):  
BernhardA Sabel ◽  
Mohamed Tawfik ◽  
Xiwei Zhang ◽  
Lisa Grigartzik ◽  
Peter Heiduschka ◽  
...  

2022 ◽  
Author(s):  
Chi Ma ◽  
Dandan Zhu ◽  
Wenyi Lin ◽  
Ying Li ◽  
Yuanzheng Huang ◽  
...  

Small interfering RNA (siRNA)-based therapeutics represent a novel and compelling drug modality, provided that safe and competent vectors are available for their delivery. Here, we report a biodegradable amphiphilic poly(aminoester)...


2011 ◽  
Vol 14 (4) ◽  
pp. 339-352 ◽  
Author(s):  
Hui Chen ◽  
Lili Chen ◽  
Lingyu Sun ◽  
Hongqun Zhen ◽  
Xiaomei Li ◽  
...  

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