Stage of Program: Candidate Discovery (DISC2, some 1.0 projects)


Drug discovery for gastrointestinal motility disorders using hPSC-derived enteric ganglioids

Research Objective Our goal is to use stem cell models to identify a small molecule drug candidate for GI motility disorders. Impact The candidate will be used for severe gastrointestinal motility disorders including chronic constipation, achalasia and gastroparesis. Major Proposed Activities Assessment of candidate compounds on stem cell derived models from diverse genetic backgrounds Evaluation […]

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 […]

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 […]

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 […]

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 […]

Orthogonal IL2 Receptor Transduced Regulatory T Cells for Clinical Application

Research Objective Genetically modified cells that help control immune reactions Impact Improved treatment for patients undergoing transplantation Major Proposed Activities To identify the optimal source of regulatory T cells for introduction of the novel IL2 receptor To test the impact of a novel IL2 protein on activating the regulatory T cells To determine the optimal […]

Developing a breast cancer stem cell drug

Research Objective To make a drug that kills breast cancer stem cells Impact Metastatic breast cancer is incurable. The goal is to make a drug leading to cures Major Proposed Activities Make a novel drug that potentially more effectively treats breast cancer with less toxicity Test the drug for efficacy and toxicity Breast cancer is […]

A First-in-Class Treatment for Progressive Multifocal Leukoencephalopathy Via Multimodal Immune System Engineering

Research Objective We propose to discover genome- and epigenome-edited allogeneic T cells engineered to selectively target JCV as a potentially lifesaving treatment for progressive multifocal leukoencephalopathy (PML). Impact If successful, we would revolutionize treatment for PML patients in whom T cell immunity cannot be restored or boosted and unable to wait for adoptive transfer of […]

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 […]

Assessing the Functional, Immunologic and Microbiologic Characteristics of Human Livers Created in Chimeric Pigs

Research Objective Generating human liver using pig as a bioreactor Impact The livers produced will be used for transplantation into patients with end-stage liver disease, metabolic disorders, and for metastatic liver disease not amenable to resection Major Proposed Activities MILESTONE 1 TASKS 1) Procure liver from control pig 2) Place on XVIVO Perfusion Device MILESTONE […]