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Science for Development Center in Xenotransplantation

Grant number: 21/11872-5
Support Opportunities:Research Grants - Science Centers for Development
Duration: June 01, 2022 - May 31, 2027
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Silvano Mario Attilio Raia
Grantee:Silvano Mario Attilio Raia
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Pesquisadores principais:
Ernesto da Silveira Goulart Guimarães ; Jorge Elias Kalil Filho
Associated researchers:Adriano Marim de Oliveira ; Beatriz Nogueira Messias de Miranda ; Cláudia Echevenguá Teixeira ; Flávia Gutierrez Motta ; Helena Corrêa de Araújo Gomes ; Luciano Abreu Brito ; Luiz Carlos de Caires Júnior ; Mayana Zatz ; Natália Neto Pereira Cerize ; Osmar Jose Santos de Moraes
Associated scholarship(s):24/02996-0 - Evaluation of hyperacute rejection of genetically modified swine skin transplant in a human model and its implications for xenotransplantation, BP.PD
24/00877-4 - Genetically Modified Pig Corneas: Histological, Optical, Biomechanical Evaluations, and In Vitro Immune Response., BP.PD
23/15073-5 - Comparative Bioinformatic Analysis of Wild Type and Edited Porcine Cells., BP.TT
+ associated scholarships 23/15538-8 - GENETICALLY ENGINEERED PORCINE CORNEAS FOR HUMAN TRANSPLANTATION, BP.PD
23/11935-2 - Pathogen surveillance for maintenance of a swine herd with "designated pathogen free" (DPF) status, BP.TT
23/11936-9 - Genomic characterization of porcines and swine cell lines: genotyping of the swine leukocyte antigen haplotypes (SLA), blood typing and detection of copy number and genic expression of porcine endogenous retroviruses (PERVs), BP.TT
23/11983-7 - Techniques for directed insertion of Human Transgenes into Clonal Lineages of Porcine Fetal Fibroblasts for Nuclear Transfer Aiming at the Production of Animals Suitable for Xenotransplantation, BP.TT
23/13344-1 - Histological, optical, biomechanical evaluations and in vitro immunological response in corneas discarded from eye banks., BP.IC
22/15373-6 - Amino acid supplementation in media, establishment of adequate physical conditions during in vitro production and standardization of electroporation in swine zygotes., BP.TT
22/15222-8 - Estabilshment of transgeneic celullar lineage of porcine model with potential immune evasion for human xenotransplant, BP.TT
22/15315-6 - Evaluation of copy number of porcine endogenous retroviruses (PERVs) in swine cell lines, BP.TT
22/11459-3 - Production and transfer of genetically modified embryos for organ donor pigs production, BP.TT
22/11014-1 - Cytokine supplementation during oocyte in vitro maturation for the production of viable cloned embryos, BP.TT
22/11147-1 - Establishment of methods for embryo cloning and gene editing in swine zygotes using micromanipulation and microinjection techniques., BP.TT
22/11022-4 - Genomic evaluation of off-target events and PERVs copies in swine cells genetically modified for xenotransplantation, BP.TT - associated scholarships

Abstract

After the development of modern genetic editing techniques, xenotransplantation became the potential solution to the shortage of organs for transplantation. Since 2017, our group has been leading a research effort for the development of genetically modified pigs for this purpose. With the support of XenoBrasil (startup that has EMS as a partner and some of the leading researchers of this project) and FAPESP, we were able, in a short period, to achieve results that place us in the position to generate the first piglets with potential for xenotransplantation of the South hemisphere. Porcine cells have been edited to inactivate the three main enzymes that triggers hyperacute rejection. Using the somatic nuclear transfer technique, the first embryos capable of being transferred to a surrogate were generated. In addition to being already working on several technological improvements to expand this pioneering initiative, we propose, through this call, the establishment of the Science Center for Development (CCD) in Xenotransplantation with support from the State Health Department. The center will allow the development of the generated technology aiming at: i) improvement of gene editing and animal embryology/cloning methodologies for the development of new strategies that will allow for an increase in xenograft survival, in the overall technical efficiency of the process and in cost reduction. ii) evaluation of several graft safety parameters related to the molecular protocols developed and the potential impact in animal health and fitness. iii) development of a robust set of in vitro and ex vivo experiments in order to assess the immune response (cellular and humoral) of the human recipient to the porcine graft. The CCD in Xenotransplantation will be a multidisciplinary association between the USP Medical School, the Biosciences Institute (IBUSP) and the Technological Research Institute (IPT), in addition to XenoBrasil. Through these partnerships, the CCD in Xenotransplantation will carry out its activities in state-of-the art laboratories, in addition to having access to a structure for raising genetically modified pigs that will be built by the IPT, with support from the São Paulo State Economic Development Department. Aware of the high complexity of the topic, we propose a communication plan that aims to attract attention and promote debate on the topic with the most diverse segments of society, in addition to academia itself. Likewise, a partnership plan was proposed to manage the activities of all institutions associated with the center, as well as attract new partners and new talent. A strategic management plan, committed to good governance practices, institutional transparency and managed by an executive committee of excellence, will be in charge of managing activities of the Center and will have the assistance of an international advisory committee, composed of world-renowned experts in the various areas of knowledge that encompasses the project. Thus, we present this proposal aiming audacious developments in xenotransplantation and placing the country in the spotlight of the world stage of technological innovations in the area, in addition to enabling the development of a robust pre-clinical dossier, aiming future clinical application. (AU)

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