Development of a platform for the delivery of nucleic acids for gene therapy using lipid nanoparticles

• Grant number: 23/13824-3
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: January 01, 2024
• End date: February 20, 2024
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Mauro Martins Teixeira
• Grantee: Maria Eduarda de Castro
• Host Institution: Instituto de Ciências Biológicas. Universidade Federal de Minas Gerais (UFMG). Ministério da Educação (Brasil). Belo Horizonte , SP, Brazil

Abstract

The development of T cells engineered to express a chimeric antigen receptor (called CART cells) has revolutionized the treatment of some types of hematological tumors. There are also important challenges to the broader use of this technology, including the time and high cost of manufacturing, the potential adverse effects associated with viral vectors and the lack of approved products against solid tumors. Several initiatives have sought to replace viral vectors with non-viral T cell transfection methods, especially the use of ionizable lipid nanoparticles (LNPs). LNPs have become more relevant since the clinical approval of platforms for mRNA and siRNA delivery. LNPs can be used to engineer T cells in vitro for transient expression of CAR or can be modified to deliver nucleic acids to specific organs or cells in vivo. This approach can be used to develop a less expensive product, in a shorter time, possibly with fewer adverse effects, and which can be modified to treat solid and hematological tumors. Our group has developed novel methodologies that allow the delivery of nucleic acids by LNPs in vitro and in vivo. We have experience in the manufacturing process of LNPs, as well as in the synthesis of unique lipids that allow the patenting of innovative processes.This project was submitted to the CNPQ, process 444101/2023-3, whose activities will begin from November 2023 and is also part of the activities of the INCT Dengue and microorganism-host interactions (CNPq 465425/2014-3). Aiming to integrate the student Maria Eduarda de Castro in this research, I propose to show how the laboratory works, since the objective of the Aristides Pacheco Leão Program is to stimulate the scientific vocation in young undergraduates, with this exposure and understanding being important for the future scientist. Furthermore, transfection techniques in human cells will be taught, the aim of which is not only to spread knowledge of what we already do, but also to plant the idea that this innovative technique can be used as a tool for various future treatments. She will also be taught how clinical vaccine trials work, so that she can understand how translational research works, in theory and in practice. (AU)