Construction of antibody expression vector containing optimized UCOI chromatin function modifying sequence

• Grant number: 24/13747-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2024
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Ana Maria Moro
• Grantee: Elton Roger da Silva Ostetti
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 20/07040-1 - Center of Research and Development in Immunobiologicals, AP.NPOP

Abstract

The unstable expression of recombinant proteins occurs in mammalian cells, especially in Chinese hamster ovary (CHO) cell lines, widely used in monoclonal antibody production. Instability in production, observed in up to 63% of recombinant CHO cell lines, is unpredictable and demands lengthy stability studies, which are costly in time and resources. One of the main factors contributing to this instability is the epigenetic silencing of the gene of interest (GOI), resulting in gene inactivation without mutation. Ubiquitous Chromatin Opening Elements (UCOE) have been studied to solve this problem, maintaining chromatin in an open state that allows stable gene expression and prevents transcriptional silencing. A2UCOE, a specific type of UCOE, has proven highly effective in improving therapeutics protein production and maintaining gene expression stability in transfected cells. This project aims to optimize A2UCOE and construct antibody expression plasmids containing the optimized element. The application of these improvements has the potential to significantly enhance industrial biotechnology, promoting more efficient and consistent production of recombinant proteins. In addition to reducing production costs and time, this can expand access to vital treatments for various medical conditions, improving quality of life and reducing public health expenditures.