Stage of Program: Basic Research and Discovery Stage Programs

A Novel Therapy for Articular Cartilage Autologous Cellular Repair by Paste Grafting

Research Objective Articular paste graft containing MSCs and an adhesive hydrogel that support cartilage growth will be combined for an effective and functional stem cell based cartilage repair procedure. Impact The proposed biologic cartilage repair therapy results in accessibility of an effective, low cost, one-step and functional biologic solution to those with cartilage injuries and […]

Transplantation of genetically corrected iPSC-microglia for the treatment of Sanfilippo Syndrome (MPSIIIA)

Research Objective This research will discover whether transplantation of stem cell-derived microglia can be used to treat Sanfilippo syndrome, a devastating and currently untreatable childhood neurological disease. Impact If successful, this research will identify a promising new therapeutic approach for Sanfilippo Syndrome and provide the first evidence that stem cell derived microglia could be used […]

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 […]

Improving the efficacy and tolerability of clinically validated remyelination-inducing molecules using developable combinations of approved drugs

Research Objective The candidate is a fixed dose binary small molecule drug combination, consisting of two agents that act synergistically on a multipotent stem cell population in the CNS to stimulate remyelination. Impact The proposed studies will address bottleneck issues related to the effect size and tolerability of clinically validated remyelination drug classes. Major Proposed […]

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 […]

Generating deeper and more durable BCMA CAR T cell responses in Multiple Myeloma through non-viral knockin/knockout multiplexed genome engineering

Research Objective We will use integrated gene editing techniques to develop a new CAR-T cell therapy for multiple myeloma treatment Impact Develop an improved CAR-T cell therapy for patients with refractory multiple myeloma and a new manufacturing strategy that circumvents the costs and inefficiencies of viral production. Major Proposed Activities Establish and optimize a CRISPR […]

Injectable, autologous iPSC-based therapy for spinal cord injury

Research Objective We propose to develop and validate a therapy for spinal cord injuries in which human stem cell-derived neural cells is injected into the injured spinal cord using an injectable gel. Impact Our study will address the critical need for an SCI treatment that significantly improves the neurological recovery and hence quality of life […]

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. […]

A novel hybrid CRISPR tool for gene network perturbation and hiPSC engineering

Research Objective A CRISPR-based tool for simultaneous up- and downregulation of many (~5-20) genes, and a computational tool using scRNA-seq data to predict which genes to perturb for efficacious cell-type conversion. Impact A critical bottleneck to the creation of specific cell types from stem cells (and related therapies) is our current inability to make cells […]

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 […]