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Gene therapy for bone regeneration using CRISPR-Cas9 system

Grant number: 16/23850-8
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): April 01, 2017
Effective date (End): March 31, 2018
Field of knowledge:Health Sciences - Dentistry - Oral and Maxillofacial Surgery
Principal Investigator:Adalberto Luiz Rosa
Grantee:Gileade Pereira Freitas
Supervisor: Jane Lian
Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: University of Vermont (UVM), United States  
Associated to the scholarship:14/26864-4 - Effect of Local Injections of Mesenchymal Stem Cells and Osteoblasts on Bone Regeneration, BP.DR

Abstract

Particular interest in the areas of maxillofacial surgery and orthopedics is the treatment of non-union fractures. Among the myriad of available treatments, cell therapy has emerged as a promising approach but according to our results, not enough to get bone regeneration. Thus, we propose the use of gene therapy to fulfill and improve this still unmet need. For this, we selected genes involved in either promotion or inhibition of osteogenesis. Among the genes involved in the bone promotion, we selected the bone morphogenetic protein 9 (BMP-9) that initiates the cartilage and bone formation. Among those involved in bone inhibition, we selected the periodontal ligament-associated protein-1 (PLAP-1) that acts as an inhibitory factor for osteogenic differentiation and bone formation. Therefore, the aim this BEPE project is to analyze in vitro the behavior of mouse bone marrow-derived mesenchymal stem cells (mBM-MSCs) overexpressing BMP-9 gene and knocking out of the PLAP-1 gene by using the CRISPR-Cas9 technique. From these data, we would open windows to propose alternative therapies for the repair of bone defects and non-union fractures situations.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FREITAS, GILEADE P.; LOPES, HELENA B.; SOUZA, ALANN T. P.; GOMES, MARIA PAULA O.; QUILES, GEORGIA K.; GORDON, JONATHAN; TYE, CORALEE; STEIN, JANET L.; STEIN, GARY S.; LIAN, JANE B.; et al. Mesenchymal stem cells overexpressing BMP-9 by CRISPR-Cas9 present high in vitro osteogenic potential and enhance in vivo bone formation. Gene Therapy, v. 28, n. 12, p. 748-759, . (19/01346-4, 16/23850-8)
FREITAS, GILEADE P.; LOPES, HELENA B.; SOUZA, ALANN T. P.; GOMES, MARIA PAULA O.; QUILES, GEORGIA K.; GORDON, JONATHAN; TYE, CORALEE; STEIN, JANET L.; STEIN, GARY S.; LIAN, JANE B.; et al. Mesenchymal stem cells overexpressing BMP-9 by CRISPR-Cas9 present high in vitro osteogenic potential and enhance in vivo bone formation. Gene Therapy, . (16/23850-8, 19/01346-4)

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