Optimization and use of chimerics macroendonucleases attempt to reverse the muscular dystrophy in canine model (GRMD)

Author(s)

José Luiz Nogueira

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD)
• Defense date: 2011-12-19

Examining board members

Carlos Eduardo Ambrosio; Luciana Relly Bertolini; Felipe Perecin

• Advisor: Carlos Eduardo Ambrosio

Abstract

The degenerative genetic diseases affect millions of children around the world. Among these diseases, muscular dystrophy, characterized as a monogenic disease can be treated at its source through gene therapy. Thus, this study proposes the correction of the gene that causes muscular dystrophy through genetic modification specific. The creation of new classes of therapeutics that can trigger rearrangements in the genomic DNA in a specific manner represents a new promise for gene therapy experiments. The technology will be used by RNA interference (RNAi) and that used to regulate gene expression post-transcriptional. The 70 Ku is a protein specific to the non-homologous recombination, RNAi was used in an attempt to mitigate the Ku70, then the prevailing expression of homologous recombination, aiming to correct the mutation that causes muscular dystrophy in dogs. For this evaluation, we use mesenchymal stem cell lines recently isolated populations derived from bone marrow mononuclear cells of young dogs affected by muscular dystrophy, presenting good results in characterization and culture. This work also provides the creation of a new specific therapy for the correction of muscular dystrophy, increased knowledge and understanding in the induction of genomic changes in cells in the development of new classes of molecular therapeutic agents have great potential in studies and treatment of various genetic and infectious diseases, degenerative or acquired. This paper presents methods for isolation and characterization of mesenchymal stem cells and the use of RNAi to promote homologous recombination between transfected DNA and genomic target DNA. (AU)

• FAPESP's process: 09/13282-9 - OPTIMIZATION AND USE OF CHIMERICS MACROENDONUCLEASES ATTEMPT TO REVERSE THE MUSCULAR DYSTROPHY IN CANINE MODEL (GRMD)
• Grantee: José Luiz Nogueira
• Support Opportunities: Scholarships in Brazil - Master