Disease Focus: Blood Disorders
Determining how age-specific heterogeneity of human hematopoietic stem cells and megakaryocyte progenitors contribute to thrombotic disease upon aging
Research Objective Our research will determine how aging of human blood stem cells leads to dramatic increases in disorders of platelets, cells that normally prevent bleeding but form harmful clots when dysregulated. Impact Our findings have the potential to inform prevention and mitigation strategies of bleeding and clotting disorders that contribute to significant morbidity and […]
Phase 2 Study of Hematopoietic Stem Cell Gene Transfer Inducing Fetal Hemoglobin in Sickle Cell Disease
Therapeutic Candidate or Device Autologous CD34+ cells transduced ex vivo with the BCH_BB694 LCR(-HS4) bGp D12shmiR lentiviral vector Indication Sickle cell disease with severe phenotype. Therapeutic Mechanism Silencing of beta-sickle globin and induction of anti-sickling fetal hemoglobin Unmet Medical Need Sickle cell is a severe disease with protean manifestations. The only curative therapy is an […]
Transplantation of CRISPR-CAS9 Corrected Hematopoietic Stem Cells (CRISPR_SCD001) in Patients with Severe Sickle Cell Disease
Therapeutic Candidate or Device CRISPR corrected blood stem cells are manufactured from persons with severe sickle cell disease and returned by transplant to the same person Indication Persons with sickle cell disease (adults and adolescents) with repeated, severe painful and lung events are eligible for the clinical trial Therapeutic Mechanism Blood stem cells are harvested […]
A Phase 1 Study of ECT-001 Expanded Cord Blood and Myeloablative Regimen with Reduced Toxicity in Patients with Severe Sickle Cell Disease.
Therapeutic Candidate or Device ECT-001 graft contains more stem and immune cells than conventional cord blood graft, leading to prompt recovery and better outcomes for patients. Indication Severe Sickle Cell Disease Therapeutic Mechanism Hematopoietic stem cell transplantation is the only cure for severe sickle cell disease. The ECT-001 expanded cord blood cells will replace the […]
Evaluation of Gene Therapy Approaches for Autosomal Recessive Hyper IgE Syndrome Due to Mutations in DOCK8
A Treatment for Artemis-deficient Severe Combined Immunodeficiency using Non-Viral CRISPR-driven Safe Harbor Transgenesis in Hematopoietic Stem Cells
Research Objective A Treatment for Artemis-deficient Severe Combined Immunodeficiency using Non-Viral CRISPR-driven Safe Harbor Transgenesis in Hematopoietic Stem Cells Impact We aim to develop a novel genome editing based therapy for Artemis-deficient severe combined immunodeficiency that would improve upon prior gene therapies in efficacy, safety, and scalability. Major Proposed Activities Discover optimal approach for nonviral […]
Therapeutics to overcome the differentiation roadblock in Myelodysplastic Syndrome (MDS)
Research Objective This proposal will deliver a small molecule therapeutic candidate for the treatment of Myelodysplastic Syndromes and will act by inducing differentiation on mutated hematopoietic stem cells. Impact This application will enable development of a therapeutic candidate for the treatment of Myelodysplastic Syndromes, a preneoplastic hematological condition of HSCs. Major Proposed Activities Determine the […]
Defining the Optimal Gene Therapy Approach of Human Hematopoietic Stem Cells for the Treatment of Dedicator of Cytokinesis 8 (DOCK8) Deficiency
Research Objective A new therapeutic option for DOCK8 deficiency using autologous human hematopoietic stem cells modified through either lentiviral gene addition or CRISPR/Cas9 based gene editing. Impact Allogeneic HSCT is complicated by comorbidities that can be addressed by autologous stem cell gene therapy. This is relevant for DOCK8 deficiency and can be applied broadly to […]
Targeted Immunotherapy-Based Blood Stem Cell Transplantation
Research Objective An engineered antibody construct that targets and recruits immune cells to kill diseased blood stem cells, including leukemia stem cells, so that healthy stem cells can replace the diseased ones Impact An antibody that can direct immune cells to kill diseased stem cells would make stem cell transplant safer, more accessible and effective […]
Hematopoietic Stem Cell Gene Therapy for Alpha Thalassemia
Research Objective The objective of this research is to define the final therapeutic candidate for effective hematopoietic stem cell gene therapy to treat severe alpha thalassemia that requires life-ling transfusions Impact Severe alpha thalassemia may lead to fetal demise or a life-long need for chronic transfusions with multiple medical complications, especially iron overload from transfusions. […]