Project Objective: Proof of Concept
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. […]
Drug Development of Inhibitors of Inflammation Using Human iPSC-Derived Microglia (hiMG)
Research Objective We will screen for modifiers of the response to misfolded αSyn and Aβ, and their cognate antibodies. Development of drugs to combat this inflammation is important in neurodegenerative diseases. Impact Inhibiting the immune response to minimize NLRP3 inflammasome activation may prevent the neurotoxic effect of activated microglia, and attenuate disease progression in neurodegenerative […]
A new precision medicine based iPSC-derived model to study personalized intestinal fibrosis treatments in pediatric patients with Crohn’s disease
Research Objective We propose to discover a tool that will utilize patient specific iPSC-derived human mini-guts to identify personalized antifibrotic treatments in pediatric Crohn’s disease patients Impact The major bottleneck in intestinal fibrosis research is the difficulty in obtaining patient-specific biologically relevant cells for in vitro modeling. This iPSC-derived tool would overcome it. Major Proposed […]
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 […]
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 […]
Modulation of oral epithelium stem cells by RSpo1 for the prevention and treatment of oral mucositis
Research Objective Locally delivered formulation of RSpo1 protein as an activator of Lgr5+ epithelial stem cells in chemotherapy- or radiation therapy-induced oral mucositis Impact Oral mucositis Major Proposed Activities RSpo1 formulation design and selection for optimal oral delivery Activation of Wnt pathway by formulated RSpo1 in-vitro Production of RSpo1 protein Oral stem cell expansion by […]
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 […]