Delivering mRNA- and RNAi-based therapies in a single treatment has the potential to fight complex diseases

Researchers at the University of Ottawa may have cracked the code for harnessing both mRNA and RNAI-based therapies to improve treatments for cancer, cardiovascular disease and other complex diseases.

The success of COVID-19 vaccines has highlighted the potential of mRNA-based therapies that selectively manipulate how genes relay their functions. On the other hand, RNA interference (RNAi) is a natural defense mechanism against exogenous genes, but it can counteract the positive effects of mRNA.

A new proof-of-concept study published in ACS Nanoscience Au shows that both mRNA and siRNA can be delivered in vivo and in vitro to enhance and inhibit expression of multiple genes and proteins to improve therapeutic outcomes. This may be the first study.

“Our research will have a profound impact on mRNA- and RNAi-based therapeutics and drug development for complex diseases such as cancer and cardiovascular disease,” said co-first author Dr. Suresh Gadde, assistant professor of medicine. said.

“In the case of cancer, mutations in tumor suppressor genes, drug resistance, and tumor recurrence are some of the main problems. Our nanoparticle strategy can address all of these in one treatment.”

RNA-based strategies have great potential in the treatment of major diseases, but are hampered by the complexity of cancer, which requires multitargeted approaches. The approaches discovered in this study in mice could ultimately lead to new therapies to treat cancer and cardiovascular diseases through mRNA transfer, RNA interference, translation inhibition, and/or translational repression. It may be possible to connect.

“Using this technology, we can restore the expression of tumor suppressor genes such as PTEN, P53, or tumor antigens for immunotherapy, while simultaneously knocking down genes/proteins involved in the development of drug resistance/CSC. ,” said Dr. Gadde, who led the study. Alongside colleagues in the Department of Cellular and Molecular Medicine, Dr. Lisheng Wang, Dr. Marceline Côté, Dr. Shireesha Manturthi, and Dr. Sara El-Sahli.

These findings will drive future research to develop nanoparticles containing therapeutic mRNAs and siRNAs as researchers study their effects in clinically translatable animal models.

“Using our approach, crosstalk can be selectively enhanced or disrupted to improve therapeutic outcomes. Through mRNA transduction, RNA interference, translational inhibition, and/or translational repression, antitumor “We can synergistically promote tumor-promoting factors while minimizing tumor-promoting factors,” he added. We will discuss the latest efforts coming out of the labs of Dr. Gadde and Dr. Wang.

Dr. Gadde’s research focuses on the development of nanotherapies to study and understand the biology of various diseases and the factors that cause their progression, as well as to develop therapeutic strategies. Meanwhile, Dr. Wang’s research focuses on cancer stem cell signaling pathways and uses cellular and molecular approaches and in vivo animal models to develop effective cancer treatments.