Researchers at the University of Ottawa have figured out how to use mRNA and RNAI-based treatments to treat complex illnesses like cancer and heart disease.
The success of COVID-19 vaccines has revealed the potential of mRNA-based therapies, which selectively alter how genes relay a function. On the other hand, RNA interference (RNAi) can negate the beneficial effects of mRNA and is a natural defense mechanism against exogenous genes.
The first proof-of-concept study to demonstrate the delivery of both mRNA and siRNA in vivo and in vitro to enhance and disrupt multiple gene and protein expressions to improve therapeutic outcomes was published in ACS Nanoscience.
Our work will have a huge impact on mRNA and RNAi-based therapies and drug development for complex diseases like cancer, and cardiovascular diseases. For cancer, mutations in tumor suppressor genes, drug resistance, and tumor reoccurrence are some of the main problems. Our nanoparticle strategies can handle all of them in a single treatment.”
Dr. Suresh Gadde, Study Co-Lead Author and Assistant Professor, University of Ottawa
The complexity of cancer, which requires multitargeted treatment strategies, has limited the effectiveness of RNA-based approaches for treating major diseases. However, the method demonstrated in this mouse study could pave the way for new treatments for both cardiovascular diseases and cancer. These treatments may utilize techniques such as mRNA introduction, RNA interference, translational inhibition, and translational repression.
By using this technology, we can restore tumor suppressor gene expressions such as PTEN, P53, or tumor antigens for immunotherapy while simultaneously knocking down the genes/proteins involved in drug resistance/CSC developments.”
Dr. Suresh Gadde, Study Co-Lead Author and Assistant Professor, University of Ottawa
These findings will fuel future research into the effects of therapeutic mRNA and siRNA nanoparticles in clinically applicable animal models.
We can use our approach to selectively enhance or interfere with cross-talks to improve therapeutic outcomes. We can synergistically promote antitumoral factors while minimizing protumoral factors via mRNA introduction, RNA interference, translational inhibition, and/or translational repression.”
Dr. Suresh Gadde, Study Co-Lead Author and Assistant Professor, University of Ottawa
Source:
Journal reference:
Manturthi, S., et al. (2024) Nanoparticles Codelivering mRNA and SiRNA for Simultaneous Restoration and Silencing of Gene/Protein Expression In Vitro and In Vivo. ACS Nanoscience Au. doi.org/10.1021/acsnanoscienceau.4c00040.
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