A biodegradable amphiphilic poly(aminoester) dendrimer for safe and effective siRNA delivery

2022 ◽  
Author(s):  
Chi Ma ◽  
Dandan Zhu ◽  
Wenyi Lin ◽  
Ying Li ◽  
Yuanzheng Huang ◽  
...  
Keyword(s):  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Interfering Rna

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)...

scholarly journals pH-sensitive zwitterionic polycarboxybetaine as a potential non-viral vector for small interfering RNA delivery

RSC Advances ◽  
2020 ◽  
Vol 10 (73) ◽  
pp. 45059-45066
Author(s):  
Huan Peng ◽  
Weihong Ji ◽  
Ruichen Zhao ◽  
Zhiguo Lu ◽  
Jun Yang ◽  
...  
Keyword(s):  
Small Interfering Rna ◽  
Viral Vector ◽  
Sirna Delivery ◽  
Ph Sensitive ◽  
Acidic Environment ◽  
Interfering Rna

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

scholarly journals Structurally modulated codelivery of siRNA and Argonaute 2 for enhanced RNA interference

2018 ◽  
Vol 115 (12) ◽  
pp. E2696-E2705 ◽  
Author(s):  
Jiahe Li ◽  
Connie Wu ◽  
Wade Wang ◽  
Yanpu He ◽  
Elad Elkayam ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Rna Interference ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Effector Protein ◽  
Side Group ◽  
Argonaute 2 ◽  
Fundamental Research ◽  
Delivery Vehicles ◽  
Interfering Rna

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.

scholarly journals Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

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
Keyword(s):  
Drug Delivery ◽  
Hyaluronic Acid ◽  
Small Interfering Rna ◽  
Drug Delivery Systems ◽  
Sirna Delivery ◽  
Delivery Systems ◽  
Low Toxicity ◽  
Interfering Rna

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.

scholarly journals Elucidating the role of surface chemistry on cationic phosphorus dendrimer–siRNA complexation

Nanoscale ◽  
2018 ◽  
Vol 10 (23) ◽  
pp. 10952-10962 ◽  
Author(s):  
Marco A. Deriu ◽  
Nicolas Tsapis ◽  
Magali Noiray ◽  
Gianvito Grasso ◽  
Nabil El Brahmi ◽  
...  
Keyword(s):  
Surface Chemistry ◽  
Structural Properties ◽  
Crucial Role ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Interfering Rna

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.

scholarly journals Switching the intracellular pathway and enhancing the therapeutic efficacy of small interfering RNA by auroliposome

2020 ◽  
Vol 6 (30) ◽  
pp. eaba5379 ◽  
Author(s):  
Md. Nazir Hossen ◽  
Lin Wang ◽  
Harisha R. Chinthalapally ◽  
Joe D. Robertson ◽  
Kar-Ming Fung ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gold Nanoparticles ◽  
Gene Silencing ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Delivery Systems ◽  
Ovarian Cancer Cells ◽  
Interfering Rna

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.

scholarly journals Small Interfering RNA- Modern Approach for Intervening Pathological Conditions

2021 ◽  
Vol 2 (2) ◽  
pp. 16-19
Author(s):  
Shazia Choudhary ◽  
Sheeba Murad ◽  
Sana Gul ◽  
Hayat Khan ◽  
Samra Khalid ◽  
...  
Keyword(s):  
Rna Interference ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Rnai Pathway ◽  
Modern Approach ◽  
Rna Molecules ◽  
Rnai Technology ◽  
Efficient Delivery ◽  
Biological Discovery ◽  
Interfering Rna

RNA interference (RNAi) refers to the inhibition of gene expression by small double-stranded RNA molecules. This technology can prove to be a breakthrough biological discovery of the decade as it has the potential to revolutionize the field of therapeutics. RNA interference (RNAi) through small interfering RNA (siRNA) is currently being evaluated for its efficacy to be used in therapeutics as well as prophylactic strategies. Many studies are being conducted across the globe to optimize the siRNA delivery systems (in terms of safe, stable and efficient delivery) in various disorders. There are a number of diseases such as autoimmune diseases, cancer associated pathological changes, bacterial and viral induced disorders, where RNAi pathway can be explored and RNAi technology can be used as a tool to intervene such abnormalities. This review is an effort to review latest advancements in the field of siRNA based therapy development and the pits and falls generally encountered in the use of this technology.

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 ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
One Pot ◽  
Modular Assembly ◽  
Assembly Strategy ◽  
Triple Play ◽  
Interfering Rna

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

Preclinical Imaging of siRNA Delivery

2016 ◽  
Vol 69 (10) ◽  
pp. 1073 ◽  
Author(s):  
Nicholas Fletcher ◽  
Aditya Ardana ◽  
Kristofer J. Thurecht
Keyword(s):  
Molecular Imaging ◽  
Clinical Application ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Preclinical Imaging ◽  
Current State ◽  
Delivery Vehicles ◽  
Significant Uptake ◽  
Interfering Rna

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.

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