Investigation of the role of ANXA1 in limb ischemia recovery and development of gene therapy with non-viral vectors

• Grant number: 23/03903-3
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2023
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Sang Won Han
• Grantee: Sang Won Han
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Cristiane Damas Gil ; Daniela Santoro Rosa

Abstract

Peripheral arterial disease affects millions of people worldwide, with an increasing impact due to the aging population and the rise of obesity. Elderly, obese, and diabetic patients face difficulties in treatment through conventional methods, highlighting the importance of minimally invasive alternative therapies. This project's primary goal is to investigate the role of ANXA1 (Annexin A1), an anti-inflammatory protein, in the recovery of limbs affected by ischemia and inflammation. ANXA1 has shown a significant role in modulating neutrophils and macrophages and in the polarization of anti-inflammatory macrophages in some experimental models. However, its role in angiogenesis and ischemic limb resolution still requires further investigation. The main objective of this proposal is to investigate ANXA1's role in promoting the recovery of limbs affected by ischemia and inflammation. Additionally, it aims to establish a gene therapy procedure for limb ischemia using non-viral vectors to be developed. Specific objectives include constructing and characterizing plasmid and minicircle vectors for ANXA1 expression, evaluating transfection efficacy in vitro and in vivo, investigating chitosomes as a nanocarrier for ANXA1 gene delivery, and assessing the efficacy of the constructed vectors in a murine model of limb ischemia. If successful, this study could provide a new therapeutic approach for treating limb ischemia and related diseases, potentially making ANXA1 a relevant gene/factor in the treatment of these conditions. (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)

GARCIA, BIANCA B. M.; MERTINS, OMAR; DA SILVA, EMERSON R.; HAN, SANG W.. Influence of the degree of arginine substitution on chitosan-N-arginine-based chitosomes: Insights for improved gene delivery systems. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 92, p. 10-pg., 2024-01-25. (20/06913-1, 21/00971-2, 15/20206-8, 22/04361-7, 23/03903-3)

GARCIA, BIANCA B. M.; DOUKA, STEFANIA; MERTINS, OMAR; MASTROBATTISTA, ENRICO; HAN, SANG W.. Efficacy of Chitosan-N-Arginine Chitosomes in mRNA Delivery and Cell Viability Enhancement. ACS APPLIED BIO MATERIALS, v. N/A, p. 11-pg., 2024-11-19. (20/06913-1, 22/04361-7, 23/03903-3, 21/00971-2)