Therapeutic/Technology: Gene Therapy, cell free
Role of ataxin-3 polyadenylation site selection in ALS neuron toxicity and disease pathogenesis
Research Objective Here we will study the role of ataxin-3 alternative polyadenylation in the pathogenesis of ALS, and test if ASOs can reduce distal polyadenylation of ataxin-3 to rescue ALS disease phenotypes Impact Our goal is to determine if ataxin-3 genetic dysregulation is a target for the development of therapies to treat ALS (Lou Gehrig's […]
Development of a VAV2 antisense oligonucleotide (ASO) treatment for ALS
Research Objective Patient specific stem cells (iPSCs) to model ALS and identify a broadly acting therapeutic intervention Impact Heterogenous patient population, dire need for broadly acting therapeutic interventions Major Proposed Activities Compare the in vitro efficacy of up to 10 lead candidate VAV2 ASOs to rescue the survival of iNs from 30 locally and nationally […]
Treatment of Myasthenic Syndrome due to Choline Acetyltransferase Deficiency Using AAV9-mediated Gene Therapy
Research Objective Use of a viral vector to transport a normal gene to children with severe motor and respiratory disabilities caused by an inborn defect of the choline acetyltransferase (ChAT) gene. Impact Treatment of an incurable disease in infants and potential amelioration of symptoms of neuro degenerative diseases with deficient cholinergic system such as Alzheimer […]
C9orf72 repeat expansion-tuned allelic suppression by CRISPRi as an ALS therapy
Research Objective We aim to discover an adeno-associated viral (AAV) CRISPRi gene therapy for amyotrophic lateral sclerosis (ALS) patients with hexanucleotide repeat expansions in the C9orf72 gene. Impact This therapy can be administered intravenously once, have long lasting effects, and is indicated for all ALS patients who carry repeat expansions of varying lengths and toxicity […]
Development of an Optogenetic Vision Restoration Gene Therapy Using an Engineered Form of Melanopsin
Research Objective The objective of this research proposal is to develop a lead AAV candidate for an optogenetic vision restoration therapy for patients suffering from blindness due to loss of photoreceptors. Impact Our optogenetic vision restoration AAV gene therapeutic candidate would non-invasively restore sight to patients terminally blinded by photoreceptors loss. Major Proposed Activities Complete […]
RNA-based therapeutics to augment regulatory T cells: a novel approach to treat myocarditis
Research Objective Use human cell therapy insights, specifically CDC-secreted EV analysis, to develop a noncoding RNA chemical entity for myocarditis treatment. Impact Key knowledge gap is how to recruit adaptive immunity to limit inflammation/heart injury in myocarditis. Boosting regulatory T cells is not yet a viable option. Major Proposed Activities Investigate the mechanism(s) by which […]
In Utero Treatment of Duchenne Muscular Dystrophy with Non-viral Gene Editing
Research Objective To develop a lipid nanoparticle/mRNA complex that can safely and efficiently edit muscle stem cells in utero, correct the dystrophin mutation, and develop a treatment for Duchenne muscular dystrophy Impact If successful, we will have developed an effective and low-cost treatment for Duchenne muscular dystrophy and a robust method to safely and efficiently […]
Gene Therapy for SLC6A8 Creatine Transporter Disorder
Research Objective The objective is to define a final therapeutic candidate for an effective gene therapy for mutations of the creatine transporter SLC6A8, a major cause of X-linked intellectual disability (ID). Impact This disorder results in severe ID, autistic-like behavior, seizures, & lack or delay of speech with no treatment. Improving brain transduction is essential […]
Novel Lipid Nanoparticles for Enhancing eNOS Synthesis for Cardioprotection Post Myocardial Infarction
Research Objective Our therapeutic candidate is a lipid nanoparticle that delivers a therapeutic dose of mRNA to the human heart, which transiently transfects of cells within the heart to improve function after an MI. Impact There is evidence for eNOS therapy as a cardioprotectant post MI; however, the progression of to the clinic has stalled […]
Modified RNA-Based Gene Therapy for Cardiac Regeneration Through Cardiomyocyte Proliferation
Research Objective Efficacious and safe intramyocardial delivery of modified mRNA encoding cell cycle regulators as a gene therapy for cardiac regeneration through resident cardiomyocyte proliferation. Impact This project would provide disease-modifying gene therapy for people with heart failure due to loss of cardiac muscle, a leading cause of deaths in the US, using novel modified […]