Evaluation of targeted rescue therapy of Polycystin-1 missense mutations in ADPKD ...
| Grant number: | 16/22061-0 |
| Support type: | Scholarships in Brazil - Post-Doctorate |
| Effective date (Start): | March 01, 2017 |
| Status: | Discontinued |
| Field of knowledge: | Health Sciences - Medicine |
| Cooperation agreement: | Coordination of Improvement of Higher Education Personnel (CAPES) |
| Principal Investigator: | Fernando Ferreira Costa |
| Grantee: | Priscila Keiko Matsumoto Martin |
| Home Institution: | Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
| Associated research grant: | 14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches, AP.TEM |
Abstract
Sickle cell disease (SCD) is a serious condition, chronic and undoubtedly represents a public health problem in Brazil. The AF is caused by a point mutation in codon 6 of the ² globin gene, leading to a glutamic acid for valine substitution and results in the production of a structurally abnormal hemoglobin, hemoglobin S. Although the cause of the disease has been known for more than fifty years, therapeutic options are still quite limited. The only drug approved for treatment is hydroxyurea and the only curative therapy is bone-marrow transplantation. The transplantation is still limited to major health care centers and for only a few patients who have compatible donors. Thus, it is necessary to develop treatments that can improve the prognosis of the disease. High levels of HbF in the blood are associated with a better clinical outcome in SCD patients. In some individuals, the expression of ³-globin gene persists into adulthood in elevated levels, which is called hereditary persistence of fetal hemoglobin (HPFH). This project is aimed at the use of a substitution of a cytosine (C) by a guanine (G) at position -195 of the globin gene ³A promoter, called non deletional HPFH Brazilian type (nd-HPFH-B), augmenting the levels of HbF. This point mutation is carried out by CRISPR system / Cas9 high fidelity, capable of performing a specific break in the DNA target sequence, thus facilitating homologous recombination of the donor sequence containing the -195 C | |