Therapeutic/Technology: Gene Therapy (All)
Developing gene therapy for dominant optic atrophy using human pluripotent stem cell-derived retinal organoid disease models
Research Objective We will develop a gene therapy for a major inherited optic nerve disease and test the effectiveness of the treatment by analyzing healthy and patient stem cell-derived mini human retinas. Impact The research will use stem cell-based methods to overcome the shortage of human retinal cells and establish disease models, thus allow testing […]
Novel antisense therapy to treat genetic forms of neurodevelopmental disease.
Research Objective We propose to discovery and evaluate antisense gene therapy for specific mutations underlying debilitating or life-threatening neurodevelopmental diseases including epilepsy and autism syndromes. Impact The conditions are four specific neurodevelopmental syndromes where mutations are well suited to ASO therapy. The bottlenecks are current lack of cellular evidence for ASOs to impact disease course. […]
AAV-dCas9 Epigenetic Editing for CDKL5 Deficiency Disorder
Research Objective We propose a gene therapy for the treatment of a severe infantile epilepsy called CDKL5 Deficiency Disorder using CRISPR-mediated epigenetic editing Impact A transformative treatment for females affected by CDKL5 Deficiency Disorder in addition a platform for the approximately 38 other X-linked intellectual disabilities that predominately affect females Major Proposed Activities Validation of […]
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 […]
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. […]
Cardiac Reprogramming Gene Therapy for Post-Myocardial Infarction Heart Failure
Research Objective The candidate is a gene therapy that delivers cardiac reprogramming factors to convert resident cardiac fibroblasts into functioning cardiac muscle. Thus, it is a regenerative cardiac gene therapy. Impact The targeted condition is heart failure arising from myocardial infarction or other insults causing focal heart muscle loss. Cardiac muscle cells are post-mitotic and […]
Development of a novel stem-cell based carrier for intravenous delivery of oncolytic viruses
Research Objective Develop a stem cell-based platform that safely and efficiently delivers viruses that specifically kill tumor cells and restore immune activity in patients with advanced cancer. Impact Overcome the inherent limitations that prevent efficient intravenous delivery of tumor killing viruses to metastatic tumors. Major Proposed Activities Compare the relative efficacy of native or cargocyte-delivered […]
Extending Immune-Evasive Human Islet-Like Organoids (HILOs) Survival and Function as a Cure for T1D
Research Objective Determine optimal islet transplant conditions and systemic treatments that promote graft survival upon transplantation into immune-competent diabetic subjects. Impact Our proposal will optimize the generation and viability of an unlimited, reproducible source of human engineered islets for transplantation. Major Proposed Activities Demonstrate improved HILO graft survival with FGF1 coating Prolong grafted HILO survival […]
Preclinical development of an exhaustion-resistant CAR-T stem cell for cancer immunotherapy
Research Objective The expected outcome is an exhaustion-resistant CAR-T cell, which persists long-term in a functional progenitor T cell state in the tumor microenvironment and can be used for cancer immunotherapy. Impact CAR-T cells are effective in B cell cancer, but less than 50% of patients experience long-term disease control. Exhaustion-resistant CARs may provide long-term […]
RNA-directed therapy for Huntington’s disease
Research Objective We develop a novel adeno-associated viral (AAV) vector-delivered RNA-targeting therapeutic for elimination of toxic RNA causative of Huntington’s disease. Impact There are no disease-modifying therapies for Huntington’s disease. Our therapeutic, if successful, will be a first-in-class treatment for this invariably fatal neurodegenerative disorder. Major Proposed Activities In vitro studies of the RNA-targeting system […]