Therapeutic/Technology: Therapeutic Approach

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 […]

Development of a new therapeutic for directing target specific stem cell migration and treatment

Research Objective A drug-stem cell combination therapy wherein the drug will direct and promote the delivery and distribution of stem cells to the disease site for the optimal therapeutic effect of the stem cells Impact Amyotrophic lateral sclerosis (ALS) and the way to deliver and enhance stem cell-based treatment of ALS Major Proposed Activities Complete […]

Human iPSC-derived chimeric antigen receptor expressing macrophages for improved cancer treatment.

Research Objective These studies will produce a new CAR-targeted iPSC-derived macrophage-based cell therapy product for treatment of refractory malignancies such as ovarian cancer. Impact These studies eliminate a bottleneck in macrophage production and enable these cells to be engineered and manufactured in a standardized, off-the-shelf manner, rather than on a patient-specific basis. Major Proposed Activities […]

A universally applicable skin sheet for Dystrophic Epidermolysis Bullosa via next-generation gene editing, iPS cell technology and tissue engineering

Research Objective We will develop a cell therapy for a rare skin disease. Patient-derived iPS cells will be genetically corrected and differentiated into epithelial sheets to be grafted on skin wounds. Impact In this proposal we will develop a universal genetic correction strategy for all COL7A1 which will be a prerequisite for the commercial viability […]

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 […]

Small Molecules to inhibit Nemo-like Kinase for Treatment of Diamond Blackfan Anemia

Research Objective We propose to study small molecules that inhibit Nemo-like Kinase, to improve the production of red blood cells in bone marrow stem cells of children with Diamond Blackfan Anemia (DBA). Impact If small molecule NLK inhibitors are identified that are effective in improving the anemia of DBA and nontoxic, then treatment and transfusions […]

Stem cell-derived extracellular vesicles to reverse radiation-induced brain injury

Research Objective These preclinical studies will discover the efficacy of stem cell-derived, nanoscale, extracellular vesicles (candidate) to treat adverse effects of cancer therapy on brain function and cognition. Impact Stem cell-derived extracellular vesicles will address the confounders of stem cells (tumors, immunorejection, immunosuppression) & mitigate debilitating side-effects of cancer therapy on the brain. Major Proposed […]

Targeting Critical Regulators of Cancer Stem Cells

Research Objective We will develop a small molecule inhibitor that blocks the growth of human pancreatic cancer and AML cancer stem cells in vitro and in vivo. Impact This work will lead to a new treatment for cancer stem cell driven diseases such as AML and pancreatic cancer. In addition, it will improve the prognosis […]

Building a hiPSC-based biopacemaker

Research Objective A proof-of-concept biopacemaker constructed by bioprinting hiPSC-derived pacemaking cells and support cells based on the blueprint of the native pacemaking tissue of a large mammalian heart. Impact A hiPSC-based biopacemaker bioprinted using a design of the native pacemaking tissue in the heart, with protective electrical and mechanical insulations, can better sustain the pacemaking […]