Therapeutic/Technology: Gene Therapy, cell free
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 […]
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 […]
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 […]
Providing a cure for sphingosine phosphate lyase insufficiency syndrome (SPLIS) through adeno-associated viral mediated SGPL1 gene therapy
Research Objective AAV-SPL 2.0 is a gene therapy cure for SPLIS, a lethal childhood disorder of metabolism that causes kidney failure. Our gene therapy may also work in more common fibrotic (scarring) kidney diseases. Impact Our treatment may cure a rare but often fatal genetic disease (SPLIS) for which no specific treatment is available. It […]
Optimization of a gene therapy for inherited erythromelalgia in iPSC-derived neurons
Research Objective The goal of this grant is to develop a gene therapy for a rare painful disorder, Inherited Erythromelalgia (IEM). Impact There are currently no FDA approved drugs for IEM, which is caused by a gain-of-function mutation in a sodium channel, Nav1.7. We propose epigenetic repression of Nav1.7 to provide a cure for IEM. […]
New noncoding RNA chemical entity for heart failure with preserved ejection fraction.
Research Objective Modified synthetic noncoding RNA molecule Impact Heart failure with preserved ejection fraction Major Proposed Activities Lead optimization Perform extensive preclinical testing and select a therapeutic candidate. Develop and test preliminary potency assays based on mechanistic insights. Demonstration of injury-modifying bioactivity in a clinically-relevant human progenitor cell population. Optimize formulation and dosing for intravenous […]
AAV9-Cas13 gene therapy for Angelman syndrome
Research Objective AAV9-Cas13 gene therapy for Angelman syndrome using a first-in-kind mechanism of action that will safely and permanently restore expression of endogenous UBE3A that is deficient in CNS neurons. Impact Angelman syndrome is a rare (1 in 15,000 births) neurogenetic disorder caused by loss of UBE3A in the brain, causing severe developmental delay, ataxia […]
Hypoxia-specific Production of Exosomes from iPSC-derivatives for Myocardial Repair
Research Objective A lead therapeutic candidate will be selected: 1) exosomes from hypoxia-injured iPSC-derived cardiomyocytes (iCMs), 2) exosomal miRNA cluster, and 3) siRNA inhibition of exosomal target gene, Notch3. Impact Effective targeted therapy to restore the injured and vulnerable myocardium is urgently needed to reduce the high mortality of HF patients. Promising discovery of iPSC […]