Human SLPI protein production in Chlamydomonas reinhardtii and its application in cardiology

• Grant number: 19/17340-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): July 01, 2021
• Effective date (End): June 30, 2023
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Augusto Ducati Luchessi
• Grantee: Karina Danielle Pereira
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated research grant: 16/12899-6 - Genomics, epigenomics and pharmacogenomics characterization of familial hypercholesterolemia in the Brazilian population, AP.TEM

Abstract

The Leukocyte Secretory Protease Inhibitor (SLPI) is a non-glycosylated cationic protein with action against serine protease, serving to control the excessive release of secreted proteases such as trypsin, chymotrypsin, elastase and cathepsin G from mammal. In addition to its antiprotease activity, SLPI has been shown to express antibacterial, antiviral, antifungal and anti-inflammatory properties. Recently, the role of recombinant human SLPI (rhSLPI) in therapy has been observed, for example, in the treatment of lung inflammation, ischemic injury, reperfusion in heart transplantation and Tuberculosis. The rhSLPI used in the current studies are produced by bacteria, however, there is a potential risk of contamination by endotoxins, limiting its use. In addition, the high cost of producing rhSLPI in bacteria indicates the need for an alternative production system. In fact, microalgae are promising biotechnological platforms for the production of a wide range of bioproducts, including recombinant proteins for pharmaceutical applications. The aim of this project is to produce rhSLPI in Chlamydomonas reinhardtii and then evaluate its therapeutic potential in the treatment of Familial Hypercholesterolemia, through its possible inhibitory action against PCSK9 serine protease, a protein with a key role in regulating the plasma concentration of lipoproteins in low density (LDL). Thus, this study can reveal the action of rhSLPI in an additional clinical context in the field of cardiology, and it can be characterized as a promising biopharmaceutical. (AU)