Preclinical Imaging of siRNA Delivery

2016 ◽  
Vol 69 (10) ◽  
pp. 1073 ◽  
Author(s):  
Nicholas Fletcher ◽  
Aditya Ardana ◽  
Kristofer J. Thurecht

Small interfering RNA (siRNA) is emerging as a class of therapeutic with extremely high potential, particularly in the field of oncology. Despite this growing interest, further understanding of how siRNA behaves in vivo is still required before significant uptake into clinical application. To this end, many molecular imaging modalities have been utilised to gain a better understanding of the biodistribution and pharmacokinetics of administered siRNA and delivery vehicles. This highlight aims to provide an overview of the current state of the field for preclinical imaging of 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.


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.


2008 ◽  
Vol 19 (2) ◽  
pp. 125-132 ◽  
Author(s):  
Antonin R. de Fougerolles

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.


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