Abstract
Ribonucleic acid interference (RNAi) is an innovative treatment strategy for a myriad of indications. Non-viral synthetic nanoparticles (NPs) have drawn extensive attention as vectors for RNAi due to their potential advantages, including improved safety, high delivery efficiency and economic feasibility. However, the complex natural process of RNAi and the susceptible nature of oligonucleotides render the NPs subject to particular design principles and requirements for practical fabrication. Here, we summarize the requirements and obstacles for fabricating non-viral nano-vectors for efficient RNAi. To address the delivery challenges, we discuss practical guidelines for materials selection and NP synthesis in order to maximize RNA encapsulation efficiency and protection against degradation, and to facilitate the cytosolic release of oligonucleotides. The current status of clinical translation of RNAi-based therapies and further perspectives for reducing the potential side effects are also reviewed.
Highlights
At the forefront of medicine, gene therapy is one of the most exciting therapeutic armamentarium developed during the past decade
Time-lapse confocal fluorescent microscopy was applied to observe the release of short interfering RNAs (siRNAs)-AF647 into the cytosol, and the results showed the number of lipid NPs (LNPs) containing endosomes were stable for over 12 min after they were uptake by different cells, suggesting the majority of siRNAs were still entrapped in the endosomes
Quantifying the ratio of cytosolic siRNA were achieved by Transmission electron microscopy (TEM) through visualizing the siRNA-gold NPs, and the results showed the endosome escape of siRNA-gold was in a sigmoidal manner both in vitro (GFP-expressing HeLa cells) and in vivo
Summary
Please cite this article as: Z. Liu, S. Wang, C. Tapeinos, G. Torrieri, V. Känkänen, N. El-Sayed, A. Python, J.T. Hirvonen, H.A. Santos, Non-viral nanoparticles for RNA interference: Principles of design and practical guidelines, Advanced Drug Delivery Reviews (2021), doi: https://doi.org/10.1016/j.addr.2021.05.018 This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Zehua Liua, Shiqi Wanga, Christos Tapeinosa, Giulia Torrieria, Voitto Känkänena, Nesma El-Sayeda, Andre Pythonb, Jouni T. Hirvonena, Hélder A. Santosa,c,* Keywords: RNA interference; non-viral nanoparticles; RNA encapsulation; leukocytes targeting; endosome escape; clinical translation.
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