Development of chitosomes for mRNA Delivery to NK cells

• Grant number: 22/04361-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): September 01, 2022
• Effective date (End): August 31, 2023
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Sang Won Han
• Grantee: Bianca Bonetto Moreno Garcia
• Supervisor: Enrico Mastrobattista
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Research place: Utrecht University (UU), Netherlands
• Associated to the scholarship: 20/06913-1 - Development of chitosomes' nanoparticles for modulation of inflammation and angiogenesis by dual delivery: an approach to gene therapy for limb ischemia, BP.DR

Abstract

Interest in the development of RNA-based therapeutics has increased in recent years with demonstrations of high efficacy of Covid-19 vaccines. The capacity for rapid development and relatively low cost for production in large scale are main advantages. The mRNA instability and inefficient in vitro e in vivo delivery of mRNA have been improved significantly by chemical alterations, improved genetic engineering and nanotechnologies. However, these parameters must be adjusted and improved to each type of cell and targeted disease. In this project we propose to study the interaction of chitosomes with mRNA and make them an efficient mRNA delivery system for transfection of NK cells for cancer treatment. The rationale for this purpose comes from our previous experience with chitosomes complexed with pDNA which showed high transfection efficiency in mammalian cells and the similarity of physicochemical properties of RNA and DNA. To achieve these goals, we will collaborate with the group of Prof. Dr. Enrico Mastrobattista (University of Utrecht, Netherlands) who has a long experience in the development of bio-nanotechnology for gene and drug delivery. With this project, we hope to gain experience working with mRNA technology and develop chitosome-derived mRNA delivery systems for NK cells. This experience will help us in the development of mRNA-chitosome systems for the treatment of hindlimb ischemia, after returning to Brazil. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MORENO GARCIA, BIANCA BONETTO; DOUKA, STEFANIA; MERTINS, OMAR; MASTROBATTISTA, ENRICO; HAN, SANG WON. Optimization of Chitosan-Lipid Hybrid Nanoparticles for mRNA Delivery. MOLECULAR THERAPY, v. 31, n. 4, p. 2-pg., 2023-05-01. (22/04361-7, 15/20206-8, 20/06913-1)