Biofactory: a scalable and novel alternative to produce a lowering hypercholesteremia risk peptide

• Grant number: 22/08580-5
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: September 01, 2022
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Aruã Mastrangelo Prudenciatti
• Grantee: Aruã Mastrangelo Prudenciatti
• Company: Prudenciatti e Ribeiro Pesquisa e Desenvolvimento Ltda - ME
• CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais
• City: Botucatu
• Associated researchers: Heloysa Amaral da Silva
• Associated research grant: 20/00013-9 - Biofactory: a scalable and novel alternative to produce a lowering hypercholesteremia risk peptide, AP.PIPE
• Associated scholarship(s): 24/00961-5 - Biofactory: a scalable alternative of peptide production to reduce the risks of high cholesterol, BP.PIPE; 23/03400-1 - Expression and purification of recombinant proteins in bacteria, BP.TT; 23/00990-2 - Biofactory: a scalable alternative of peptide production to reduce the risks of high cholesterol, BP.TT; 22/12514-8 - Biofactory: a scalable alternative of peptide production to reduce the risks of high cholesterol, BP.PIPE

Abstract

In agreement with worldwide initiatives to solve this pain by pharmaceutical companies such as Novartis and AstraZeneca, we aim to promote an alternative therapy for hypercholesterolemia. During phase 1 of this project, we developed peptide analogues (tELH6A and tELH6A) in Homologous modeling to domain A of growth factor precursor homology epidermal (EGF-A) of the low-density lipoprotein receptor (LDL-R) to act as a protein convertase inhibitor subtilisin/Kexin type 9 (PCSK9) agent responsible fordys regulation and the consequent increase in plasma LDL-C. The peptides developed were optimized through bioinformatics to 1. provide resistance to proteases; 2. detain stability increased serum; 3. Possibility of oral drug abuse. Secretory clones of the peptides of interest in bacteria and tomato plants cv. M82. Milestones were reached purification, proteomic evaluations and cellular toxicity analyses. After validating with 47 market players - doctors, patients, investment funds and pharmaceuticals and signing of term sheet - the necessary technological milestones were determined so that the follow-up development would result in a proof of concept robust enough to enable the gains on investments from other funds and technology transfer conversations with the industry. In hands with this market opportunity and aware of the pain of these doctors and patients, this phase 2 is proposed to reach the milestones of a. optimize expression in organisms family members to the pharmaceutical industry; B. successfully purify the peptides of interest c. accomplish in vitro bioactivity analyses such as tissue penetrability, affinity against the target molecular (effectiveness) and cellular toxicity (safety) and c. to evaluate in vivo oral absorption and effectiveness via oral and intravenous administration in mice. The results, if positive, can enable us to serve a market valued at US$17 billion and a CAGR of 17.6% per year. The study will be conducted at Crop® Biotechnology in partnership with the State University Paulista (UNESP). (AU)