Application of synthetic biology in the construction of genetic circuit to improve the antitumor effect of Salmonella spp.

• Grant number: 18/03274-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2018
• End date: February 29, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Rafael Silva Rocha
• Grantee: Kauan Ribeiro de Sena Gomes
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 12/22921-8 - Synthetic biology approaches for deciphering the logic of signal integration in complex bacterial promoters, AP.JP
• Associated scholarship(s): 19/00478-4 - Development of an engineered microbe for inflammation sensing in the intestinal environment, BE.EP.MS

Abstract

One of the major limitations of antitumor therapy is the lack of selectivity of therapeutic agents to tumor cells. Current efforts focus on the discovery and development of drugs that selectively attack only cancer cells, while sparing normal cells. The use of bacteria as oncolytic agents is one of the innovative approaches in the treatment of cancer. These accumulate and grow preferentially within the tumor tissue, indicating a microenvironment favoring the survival and/or growth of some bacterial species and strains. In addition, current chemotherapy regimens have limited efficacy due to systemic toxicity and the emergence of resistance to therapy, preventing the use of more aggressive dosages. The bacterium Salmonella spp. is able to overcome these limitations because of its natural ability to accumulate in tumors, to actively penetrate neoplastic tissue and to be engineered to produce antitumor compounds in situ. Using Synthetic Biology, it is possible to engineer systems endowed with the strict spacial-time control of protein expression. Accurate activation of the expression may enhance the concentration of oncolytic agents within the tumor mass, mitigating the occurrence of adverse effects. Through the construction of a synthetic genetic circuit, the present project aims to obtain a lineage of Salmonella capable of activating the synthetic system in response to specific external signals of the tumor microenvironment (hypoxia) and that of a specific inducer (salicilate). The logic gate allows precise control of the location and timing of cytotoxic expression, and ensures the efficacy and safety of the treatment with this Salmonella strain. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

GOMES, Kauan Ribeiro de Sena. Application of synthetic biology in the construction of a genetic circuit to improve the anti-tumor effect of Salmonella spp. 2020. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.