As a general rule, DNA is transcribed into single-stranded RNA which is then used to manufacture proteins. The original DNA of a cell is generally set and can not be easily edited however RNA is a dynamic process in which the single-stranded ‘message-carrier’ is constantly created, used, and destroyed. By applying messenger RNA (mRNA for transcription) of a wanted protein and silencing RNA (siRNA which selectively binds to specific coding of mRNA to prevent it from being converted to a protein) it is possible to control the expression of genes at a cellular level for a fixed period of time. Researchers at University of Ottawa used mPEG-PLGA (AK026) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles for the simultaneous delivery of mRNA and siRNA to control gene/protein expression. This research holds promise to provide for treatment of a wide range of diseases. Read more: Manturthi, Shireesha, Sara El-Sahli, Yuxia Bo, Emma Durocher, Melanie Kirkby, Alyanna Popatia, Karan Mediratta et al. "Nanoparticles co-delivering siRNA and mRNA for simultaneous restoration and silencing of gene/protein expression in vitro and in vivo." bioRxiv (2024): 2024-06. https://www.biorxiv.org/content/10.1101/2024.06.22.600196.abstract
“RNA-based agents such as siRNA, miRNA, and mRNA can selectively manipulate gene expression/proteins and have the potential to revolutionize the current therapeutic strategies for various diseases, including cancer. To address the poor stability and inherent limitations of RNA agents, nanoparticle (NP) platforms have been developed to deliver functional mRNA or siRNA inside the cells. Recent studies have focused on either siRNA to knock down proteins causing drug resistance or mRNA technology to introduce tumor suppressors. However, complex diseases like cancer need multi-targeted approaches to selectively target multiple gene expressions/proteins. In this proof-of-concept study, we developed co-delivery nanoparticles containing Luc-mRNA and siRNA-GFP as model RNA agents ((M+S)-NPs) and assessed their effects in vitro and in vivo. Our studies show that NPs can effectively deliver both functional mRNA and siRNA together, simultaneously impacting the expression of two genes/proteins in vitro. Additionally, after in vivo administration, co-delivery NPs successfully knocked down GFP while introducing luciferase in a TNBC mouse model, indicating our NPs have the potential to develop RNA-based anticancer therapeutics. These studies pave the way to develop RNA-based, multitargeted, multi-delivery approaches for complex diseases like cancer. Keywords: nanoparticles, siRNA, mRNA, co-delivery, gene, protein, restoration and knockdown.”
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