Disease Focus: Metabolic Disorders

Preclinical development of an immune evasive islet cell replacement therapy for type 1 diabetes

Research Objective We will produce a universal donor cell (UDC) line by gene editing an embryonic stem cell line. Cell therapies produced from the UDC line will not be rejected by a patient’s immune system. Impact The UDC line will address the bottleneck of patient immunity that is currently slowing development of many potential cell […]

Development of immune invisible beta cells as a cell therapy for type 1 diabetes through genetic modification of hESCs

Research Objective Development of hESC-derived pancreatic beta cells that are protected from allogeneic and autoimmune attack into a cell therapy for type 1 diabetes (T1D) Impact Cell therapy of T1D is challenged by immune rejection. Therefore, we will develop pancreatic progenitors derived from genetically modified hESCs that can evade allogeneic and autoimmune responses. Major Proposed […]

Preclinical development of AAV vector-mediated in vivo hepatic reprogramming of myofibroblasts as a therapy for liver fibrosis

Research Objective An intravenously injectable virus that converts the scar cells responsible for liver cirrhosis into the cells that provide most of the liver’s function, thereby preventing or reversing liver failure. Impact The proposed research will develop a new therapy for liver cirrhosis, which can be cured by liver transplantation, but there are not enough […]

Designing a cellular niche for transplantation of human embryonic stem cell-derived beta cells

Research Objective The expected outcome of these studies is a cellular therapeutic for Type I Diabetes: engineered human islets for transplant into patients, surpassing the function of beta cells or progenitors alone. Impact The proposed studies would address key bottlenecks in cell replacement therapy for Type I Diabetes — issues with cellular engraftment, survival, and […]

Preclinical development of human hepatocyte progenitor cells for cell therapy

Research Objective Determine if human hepatocyte progenitor cells, which exist in the normal adult liver, can be maintained and expanded in vitro while maintaining in vivo regenerative capacity. Impact Cell transplantation therapy can be an effective alternative treatment for severe liver diseases to liver transplantation, which is severely limited by the lack of available donor […]

Thin Film Encapsulation Devices for Human Stem Cell derived Insulin Producing Cells

Research Objective We propose to develop a macroencapsulation technology, based on flexible nanoporous thin films, to support the long term viability and function of human stem cell derived insulin producing cells. Impact Encapsulation devices that maintain function of stem cell derived islets can address challenges with current cell therapy for Type I Diabetics, including islet […]

Developing a personalized approach to beta cell replacement for patients with a genetic form of diabetes

Research Objective To correct a gene mutation in a patient's stem cells and produce functional replacement cells for the patient to cure their diabetes. Impact WE expect that this project can serve as a model for developing new treatments for patients with certain forms of genetic diabetes. Major Proposed Activities To understand how the patient's […]

Generation of bile duct-competent transplantable human liver organoids

Research Objective Generation of human stem cell-derived mini livers capable of exporting bile into the gallbladder after transplantation into the liver Impact Mini livers capable of normal bile export would have potential for therapy of diseases in which bile export is impaired like Alagille syndrome Major Proposed Activities Generation of mini livers using human stem […]

Ex Vivo Modified Hematopoietic Stem Cells to Treat Danon Disease

Translational Candidate The candidate is CD34+ HSPCs transduced ex vivo with a LAMP2 lentiviral vector. Area of Impact Danon Disease, Lysosomal Storage Diseases, Drug Development for Rare Disease Mechanism of Action Engrafted HSPC progeny will supply normal LAMP2B to the heart, liver, muscle, and brain via lysosomal cross-correction. Specifically, macrophages transfer lysosomes containing LAMP2B to […]

Development of a Gene Therapy for the Treatment of Arginase Deficiency – Translating from Proof of Concept to Support Pre-IND Meeting

Translational Candidate Adeno-associated viral vector serotyped for hepatic tropism to express Arginase 1 in hepatocytes. Area of Impact Developing a new therapy for Arginase Deficiency, where present day this is minimally effective at best. Mechanism of Action The proposed clinical candidate is a virus that has been altered to carry the gene for & produce […]