Development of a new viral vector based on Zika virus for gene therapy

• Grant number: 22/15936-0
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: May 01, 2023
• End date: February 29, 2024
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Diego Grando Módolo
• Grantee: Diego Grando Módolo
• Company: Vyro Biotherapeutics Pesquisa e Desenvolvimento Produtos Biotecnológicos
• CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais ; Atividades profissionais, científicas e técnicas não especificadas anteriormente
• City: São Paulo
• Pesquisadores principais: Carolini Kaid Dávila
• Associated researchers: Caroline Lima dos Santos ; Pedro Henrique Machado Rodrigues ; Thais Peron da Silva
• Associated scholarship(s): 23/04614-5 - Development of a viral vector with tropism for the central nervous system, BP.TT; 23/04613-9 - Development of a new viral vector based on Zika Virus for gene therapy, BP.PIPE

Abstract

The ZIKA virus (ZIKV) has the ability to cross the blood-brain barrier and selectively infect cells of neural origin, especially in the fetal phase. ZIKV has a tropism for the CNS, making it an attractive tool for the development of a viral vector for the delivery of genes in the treatment of several diseases, including neurodegenerative diseases, whose economic cost associated with the treatment is high. Since viral vectors have proven to be more efficient in delivering genes in vivo than synthetic nanoparticle and liposome vectors, and considering the vast knowledge of the ZIKV sequence, its mechanism and natural features such as CNS tropism and infection of cells of origin neural network, Vyro Biotherapeutics has developed an mRNA, based on the structure of the ZIKA virus, to generate a new class of viral vectors, with selective tropism for the CNS and sexual organs, which will supply the gene of interest to the target cell. The unprecedented proposed viral vector has unique characteristics that are absent in available technologies, such as low immunogenicity, with natural tropism for the CNS and eyes, with the ability to overcome the blood-brain barrier (Blood brain to deliver a gene of interest of up to 10 kb, something extremely innovative, given that the size limit of available viral vectors is 4.5 kb. Considering the manufacturing of upstream viral vectors and the clinical safety of the technology, Vyro also will produce a virus-like particle (VLP) derived from the transfection of only plasmids in cultured cells to obtain ZIKVV without viral infection, with non-self-replicative characteristics, that is, unable to replicate within the target cell, attributing greater security to the technology. Therefore, as unique characteristics of the technology here evidence its innovative potential for the gene therapy market. At the end of the development As part of the proposed project, Vyro will have a unique viral vector, safe due to its natural stability and with high gene delivery efficiency to the CNS, eyes and sexual organs and retina, a potential that no delivery system has reached so far. The development of a viral vector using the Zika Virus would be a revolutionary advance, especially for neurodegenerative diseases, since the efficiency of drug delivery to the CNS is 0.01 - 0.1%, and the ZIKV delivery potential is at least 20%. (AU)