Therapeutic/Technology: Gene Therapy, cell free
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 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 […]
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 […]
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 […]
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 […]
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 […]