While stem cell and gene therapy research has advanced dramatically in recent years, many unknowns and questions remain about how best to use these approaches to develop therapies.

Nineteen research programs awarded

The governing Board of the California Institute for Regenerative Medicine (CIRM) has approved almost $25 million for 19 early‑stage discovery projects. These awards come from CIRM’s DISC2 Quest program, which supports the discovery of new stem cell‑based and gene‑therapy technologies that could be translated into treatments and improve patient care.

“Every therapy that helps save or change lives begins with a researcher asking, ‘What if?’” says Dr. Maria T. Millan, President and CEO of CIRM. “Our Quest awards show the importance of supporting early‑stage research to deepen our understanding of stem cells and their potential.”

Blood disorder

Dr. Judy Shizuru at Stanford University has received $1.34 million to develop a safer, less‑toxic form of hematopoietic stem cell transplant (HCT). HCT is the only proven cure for many blood disorders that affect people of all ages, sexes, and races. Current methods use chemotherapy or radiation to destroy a patient’s unhealthy blood stem cells. This approach is toxic, complex, and available only at major medical centers, limiting access for poor and underserved communities.

Dr. Shizuru proposes creating an antibody that prompts the patient’s own immune cells to kill diseased blood stem cells. This strategy could make stem cell transplant safer, more effective, and more accessible for people in rural or remote areas.

Ovarian cancer

Dr. Lili Yang at UCLA has received $1.4 million to develop an off‑the‑shelf cell therapy for ovarian cancer. Ovarian cancer causes more deaths than any other cancer of the female reproductive system.

Dr. Yang uses invariant natural killer T cells (iNKT), immune cells that can attack cancer. These cells are rare in the blood, so current methods require collecting them from each patient and expanding them in the lab. This process is slow, expensive, and less effective when a patient’s own cells are weakened by cancer.

In this new study, Dr. Yang will use healthy donor cord‑blood cells and genetically engineer them into an iNKT cell therapy that targets ovarian cancer. This DISC2 award will support the development and testing needed to move the therapy toward the translational stage.

Heart-related research

Timothy Hoey and Tenaya Therapeutics Inc. have received $1.2 million to test a gene‑therapy approach that replaces heart cells damaged by a heart attack. Heart disease is the leading cause of death in the U.S., with the highest rates among African Americans. It occurs when functional heart muscle cells are damaged or die, usually after a heart attack. Because these cells cannot regenerate, the damage is permanent.

Dr. Hoey’s team is developing a gene therapy that patients can receive via injection. The therapy aims to turn cardiac fibroblasts into functioning heart muscle cells that replace those lost during the heart attack. Fibroblasts are cells that can form scar tissue.

List of DISC2 Quest awards

APPLICATION NUMBER	TITLE OF PROGRAM	PRINCIPAL INVESTIGATOR	AMOUNT
DISC2-13400	Targeted Immunotherapy-Based Blood Stem Cell Transplantation	Judy Shizuru, Stanford University	$1,341,910
DISC2-13505	Combating Ovarian Cancer Using Stem Cell-Engineered Off-The-Shelf CAR-iNKT Cells	Lili Yang, UCLA	$1,404,000
DISC2-13515	A treatment for Rett syndrome using glial-restricted neural progenitor cells	Alysson Muotri, UC San Diego	$1,402,240
DISC2-13454	Targeting pancreatic cancer stem cells with DDR1 antibodies.	Michael Karin, UC San Diego	$1,425,600
DISC2-13483	Enabling non-genetic activity-driven maturation of iPSC-derived neurons	Alex Savtchenko, Nanotools Bioscience	$675,000
DISC2-13405	Hematopoietic Stem Cell Gene Therapy for Alpha Thalassemia	Don Kohn, UCLA	$1,323,007
DISC2-13507	CAR T cells targeting abnormal N-glycans for the treatment of refractory/metastatic solid cancers	Michael Demetriou, UC Irvine	$1,414,800
DISC2-13463	Drug Development of Inhibitors of Inflammation Using Human iPSC-Derived Microglia (hiMG)	Stuart Lipton, Scripps Research Inst.	$1,658,123
DISC2-13390	Cardiac Reprogramming Gene Therapy for Post-Myocardial Infarction Heart Failure	Timothy Hoey, Tenaya Therapeutics	$1,215,000
DISC2-13417	AAV-dCas9 Epigenetic Editing for CDKL5 Deficiency Disorder	Kyle Fink, UC Davis	$1,429,378
DISC2-13415	Defining the Optimal Gene Therapy Approach of Human Hematopoietic Stem Cells for the Treatment of Dedicator of Cytokinesis 8 (DOCK8) Deficiency	Caroline Kuo, UCLA	$1,386,232
DISC2-13498	Bioengineering human stem cell-derived beta cell organoids to monitor cell health in real time and improve therapeutic outcomes in patients	Katy Digovich, Minutia, Inc.	$1,198,550
DISC2-13469	Novel antisense therapy to treat genetic forms of neurodevelopmental disease.	Joseph Gleeson, UC San Diego	$1,180,654
DISC2-13428	Therapeutics to overcome the differentiation roadblock in Myelodysplastic Syndrome (MDS)	Michael Bollong, Scripps Research Inst.	$1,244,160
DISC2-13456	Novel methods to eliminate cancer stem cells	Dinesh Rao, UCLA	$1,384,347
DISC2-13441	A new precision medicine based iPSC-derived model to study personalized intestinal fibrosis treatments in pediatric patients with Crohn’s disease	Robert Barrett Cedars-Sinai	$776,340
DISC2-13512	Modified RNA-Based Gene Therapy for Cardiac Regeneration Through Cardiomyocyte Proliferation	Deepak Srivastava, Gladstone Institutes	$1,565,784
DISC2-13510	A hematopoietic stem-cell-based approach to treat HIV employing CAR-T cells and anti-HIV broadly neutralizing antibodies	Brian Lawson, The Scintillon Institute	$1,143,600
DISC2-13475	Developing gene therapy for dominant optic atrophy using human pluripotent stem cell-derived retinal organoid disease model	Xian-Jie Yang, UCLA	$1,345,691