Application of mRNA technology in the treatment of lung cancer

• Grant number: 24/21055-2
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Fernando Moreira Simabuco
• Grantee: Fernando Moreira Simabuco
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Aparecida Sadae Tanaka ; Carlos Frederico Martins Menck ; Guilherme Baldo ; ROSELENA SILVESTRI SCHUH ; Thales Papagiannakopoulos
• Associated scholarship(s): 25/21587-7 - Application of mRNA technology in the treatment of lung cancer in in vivo and in vitro models, BP.DR

Abstract

mRNA-based technology, winner of the 2023 Nobel Prize, has revolutionized medicine in recent years, being a fast and effective technique to develop efficient mRNA-based vaccines and saving millions of lives during the COVID-19 pandemic. mRNA technology has already been applied in more than 100 clinical trials for cancer therapy and the pharmaceutical industry now has a new tool to advance precision medicine in the near future. Lung cancer is a major public health problem, being the leading cause of cancer death in the world. The high mortality rate is reflected by the limited opportunity for therapy, which is restricted to the use of chemotherapeutics such as cisplatin, which commonly has associated chemoresistance. The NRF2/KEAP1 pathway is altered in several types of cancer, leading to metabolic reprogramming, adaptations to oxidative stress, and resistance to different programmed cell deaths and chemotherapy. This project aims to use mRNA technology to overexpress KEAP1, the main inhibitor of the NRF2 pathway, in lung cancer cells, causing a redox imbalance in tumor metabolism that would lead to inhibition of cancer growth and cell death. The KEAP1 mRNA will be complexed to customized nanolipid particles and tested for selected lung cancer targets in a Phage Display approach. The use of KEAP1 mRNA should be able to sensitize lung cancer cells to cisplatin since the NRF2 pathway has been associated with chemoresistance by previous studies including from our group. The results derived from this project may contribute to lung cancer therapy and mRNA-based gene therapy in the medical and biotechnology fields. (AU)