Fetal hemoglobin induction as a treatment strategy for sickle cell anemia using gene therapy

• Grant number: 22/07503-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2022
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Vanderson Geraldo Rocha
• Grantee: Felipe Augusto Rós
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID

Abstract

The feasibility of gene therapy for sickle cell anemia (SCA) represents a curative treatment alternative for patients who are candidates for hematopoietic cell transplantation (HCT) but do not have an HLA-matched donor. This therapeutic modality is based on the genetic editing of autologous hematopoietic stem cells and progenitor cells. The main strategies employed include the addition of a non-sickle ¿-globin gene, the correction of the sickle mutation, or the induction of ¿-globin expression. The induction of ¿-globin can be achieved by adding an extra ¿-globin gene, inhibiting transcription factors that block ¿-globin expression, adding fusion proteins that reactivate ¿-globin expression, or generating mutations found in individuals with fetal hemoglobin (HbF) persistence. Currently, there are two gene therapy products approved by the FDA for SCA: Casgevy (Vertex Pharmaceuticals Inc.) and Lyfgenia (Bluebird Bio Inc.). However, access is limited due to the high cost of treatments, which are priced at $2.2 million and $3.1 million per patient for Casgevy and Lyfgenia, respectively. Therefore, the development of new strategies and gene therapy products is essential to enable access for SCA patients in middle- and low-income countries. In this context, this project will analyze the effects of the artificial activation of ¿-globin gene expression using GG1-VP64 as a strategy to increase HbF production in vitro. The results can facilitate the progression of the technology to the preclinical phase.

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)

TOZATTO-MAIO, KARINA; ROS, FELIPE A.; WEINLICH, RICARDO; ROCHA, VANDERSON. Inflammatory pathways and anti-inflammatory therapies in sickle cell disease. HEMASPHERE, v. 8, n. 12, p. 11-pg., 2024-10-01. (22/07503-7, 13/08135-2)

ROS, FELIPE AUGUSTO; COUTO, SAMUEL CAMPANELLI FREITAS; MILHOMENS, JONATHAN; OVIDER, IAN; MAIO, KARINA TOZATTO; JENNIFER, VIVIANE; RAMOS, RODRIGO NALIO; PICANCO-CASTRO, VIRGINIA; KASHIMA, SIMONE; CALADO, RODRIGO T.; et al. A systematic review of clinical trials for gene therapies for ,B-hemoglobinopathy around the world. CYTOTHERAPY, v. 25, n. 12, p. 7-pg., 2023-11-17. (13/08135-2, 20/07055-9, 22/07503-7)