High capacity adenoviral vetor development expressing HSVtk and IL-12 expression cassette optimized under control of calcitonin promoter

• Grant number: 21/03418-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2021
• End date: March 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Rodrigo Esaki Tamura
• Grantee: Natália Meneses Araújo
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated research grant: 19/15619-2 - Development of high capacity adenoviral system expressing antitumoral genes, AP.JP

Abstract

Gene therapy using viral vectors has a great potential, which is already being used in human clinical protocols. Medullary thyroid carcinoma represents the thyroid malignancy with worst prognosis, featuring great clinical relevance and an ineffective treatment. The development of new therapies, including gene transfer, could be a good option. The Herpes simplex thymidine kinase (HSVtk) gene has already been applied in different kinds of suicide genes, promoting celular death in combination with ganciclovir. Interleukin (IL) - 12 gene is another gene approached in this study, which presents immunomodulatory activity. An optimized version of this gene with higher activity will be utilized. Thereby, an expression cassette containing both genes [IL-12 and HSVtk] is a great experimental model to show the efficacy and the high genetic insertion capacity of the third generation adenoviral vector (Ad-HD) to be developed in this Jovem Pesquisador project. This vector will be able to promote the expression cassette insertion in a better way compared to first generation adenoviral vector insertion capacity. Besides that, AD-HD has a prolonged ability to express the transgene of interest and consequently, may promote a more effective antitumor activity. The expression of both genes will be controlled by calcitonin promoter, limiting the action on medullary thyroid carcinoma cells, which features the high activation of calcitonin gene as a characteristic. This project presents a great clinical relevance due to a combination of different approaches in search for the worst prognosis treatment. (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)

NATÁLIA MENESES ARAÚJO; ILEANA GABRIELA SANCHEZ RUBIO; NICHOLAS PIETRO AGULHA TONETO; MIRIAN GALLIOTE MORALE; RODRIGO ESAKI TAMURA. The use of adenoviral vectors in gene therapy and vaccine approaches. GENETICS AND MOLECULAR BIOLOGY, v. 45, n. 3, 2022-10-07. (19/15619-2, 20/08271-7, 21/02659-6, 21/03418-2)