Description of Research Expertise

Dr. Breda’s work is focused on developing genetic therapies for the cure of conditions such as Sickle Cell Disease (SCD) and β-Thalassemia, also known as hemoglobinopathies. At the moment, patients with SCD and β-Thalassemia undergo palliative care to overcome anemia and the multiple comorbidities acquired over time. The gene therapy approach, instead, represents a potential definitive cure for the patients, as it targets directly the underlining cause of the diseases. Dr. Breda engineered and tested a battery of gene therapy tools to restore the production of hemoglobin, the oxygen carrier protein that is inadequate in the red blood cells of patients with hemoglobinopathies. By using lentiviral vectors, complex vehicles she developed to carry and permanently transfer the β-like globin gene in hematopoietic stem cells (HSC), she showed how patients’ cells treated can recover hemoglobin production, in both SCD and β-Thalassemia. She established a procedure that can reproducibly measure the increase of hemoglobin synthesis in red blood cells with different genetic variants upon gene therapy. From this screening a leading candidate has been selected. As a result, Dr. Breda identified and co-authored a patent for a new lentiviral vector, named ALS20, which received IND approval by the FDA in March 2023. A clinical trial based on this product is under way at CHOP. In an effort to expand access and reduce the toxicity related to current gene therapy ex vivo procedures, Dr Breda developed a system to deliver mRNA cargos to human HSC in murine models, showing that it is possible to reach and modify the fate of HSC with a single intravenous injection. Using an Cas9-modified base editing cargo, she was able to apply this technology to human sickle cells, correcting the genetic mutation that causes sickle cell disease and preventing sickling of cells. This technology could potentially allow many more patients (such as those with too many medical comorbidities to be eligible for current therapies) to undergo gene-therapy/editing.