National production of genetically modified pigs for organ xenotransplantation in humans

• Grant number: 18/14275-5
• Support type: Research Grants - Research Partnership for Technological Innovation - PITE
• Duration: October 01, 2019 - September 30, 2022
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal researcher: Silvano Mario Attilio Raia
• Grantee: Silvano Mario Attilio Raia
• Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Company: EMS S/A
• CNAE: Atividades de atenção à saúde humana não especificadas anteriormente
• CNAE: Atividades de atenção à saúde humana não especificadas anteriormente
• City: HortolândiaSão Paulo
• Principal researchers: Jorge Elias Kalil Filho ; Maria Rita dos Santos e Passos Bueno ; Mayana Zatz
• Assoc. researchers: Ernesto da Silveira Goulart Guimarães ; Luciano Abreu Brito ; Luiz Carlos de Caires Júnior
• Associated grant(s): 19/09467-5 - Multi-User Equipment approved in grant 18/14275-5: Micromanipulator - equipment for nuclear transfer, AP.EMU; 19/09474-1 - Multi-User Equipment approved in grant 18/14275-5: Nucleofector 4D - equipment used for genomic editing, AP.EMU
• Associated scholarship(s): 20/11523-8 - Establishment of porcine transgenic cell line with potential for immune escape forxenotransplantation in humans, BP.PD; 20/08726-4 - Computational comparative analysis of human and swine leukocyte antigens (HLA/SLA) and its implications in xenotransplantation, BP.PD

Abstract

Motivated by the growing need for transplantation-available organs and the latest developments in genomic editing technologies such as the CRISPR-Cas9 system, significant progress in the efficiency and safety of xenotransplantation techniques has been achieved in the last two years. Genetically engineered pigs developed to prevent receptor hyperacute immune rejection have been successfully developed in other countries. However, the possibility of cross-infection of pathogens such as PERVs (porcine endogenous retrovirus) must be controlled before the starting of therapeutic trials in humans. This project proposes the innovative national production of genetically modified pigs where genes known as inducers of hyperacute rejection (GGTA1 / CMAH / ²4GalNT2) will be knocked out. Furthermore, the copies of the PERV pol gene will be inactivated from the porcine genomic DNA. To this end, this project associates geneticists, immunologists, surgeons and clinicians with known experience and credibility in their respective area of knowledge for the development of a national biotechnological based product. At the very end, we aim to provide the population in waiting list for transplants a viable alternative and definitive therapy, thus shortening the suffering of the patients and their families. Furthermore, besides technological aspects, the viability of xenotransplantation in Brazil will require great efforts to conciliate ethical, religious and legal aspects. On this respect, our previous experience as a pioneer of intervivos liver transplantation in the world in the 80s will be extremely valuable. (AU)