
Donald B. Kohn, M.D.
Bio
Donald B. Kohn, M.D., studies the biology of blood stem cells, which are located in the bone marrow and have two important properties: they can duplicate themselves and they can create all types of blood cells. Over the course of 30 years of research, Kohn has developed new clinical methods to treat genetic blood diseases using blood stem cells that have been modified to remove genetic mutations.
Kohn’s blood stem cell gene therapy method collects some of a patient’s own blood stem cells and either adds a good copy of the defective gene or fixes the broken genes to eliminate disease-causing mutations. The patient then receives a transplant of their own corrected stem cells, which will ideally create an ongoing supply of healthy blood cells. Importantly, this method eliminates the risk of rejection associated with receiving a bone marrow transplant from a different person, meaning the patient doesn’t have to take a lifelong supply of anti-rejection drugs.
Kohn’s clinical trials for adenosine deaminase-deficient severe combined immunodeficiency (also known as ADA-SCID or bubble baby disease), a condition where babies are born without an immune system and often don’t survive past the first two years of life, have cured more than 50 babies to date. Babies with the condition and their families have traveled to UCLA for this life-saving treatment from as far away as Lebanon and a new company was formed in 2016 to further develop the therapy and make it available at other centers and to more patients.
Kohn is now applying similar blood stem cell gene therapy techniques in clinical trials for two other diseases. One of these diseases is X-linked chronic granulomatous disease, a rare inherited immunodeficiency disorder that prevents white blood cells from effectively killing foreign invaders such as bacteria, fungi or other microorganisms. If untreated, patients often succumb to chronic granulomatous disease within the first decades of life.
The second disease is sickle cell disease, the most common inherited blood disorder in the United States. This disease causes abnormal ‘sickle-shaped’ red blood cells that block small blood vessels and do not provide the appropriate amount of oxygen to the body, resulting in debilitating pain and organ damage. Kohn’s clinical trial seeks to overcome or repair the genetic mutation that causes this devastating disease, which impacts millions worldwide.
Kohn earned his bachelor’s and master’s degrees from the University of Illinois, Champaign-Urbana and his medical degree from the University of Wisconsin School Of Medicine. He completed a pediatric internship and residency in Wisconsin followed by a medical staff fellowship in the Lymphoid Malignancies Branch (formerly the Metabolism Branch) of the National Cancer Institute.
Kohn began working on gene therapy as a fellow at the National Institutes of Health in 1985 and then began practicing as a pediatric bone marrow transplant physician at Children’s Hospital Los Angeles in 1987. While practicing at Children’s Hospital Los Angeles, he started his own lab focused on stem cell research and has continued this work, advancing new therapies from the lab to the clinic.
Publications
- Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapyPublished in Cell on Tuesday, November 16, 2021
- Long-term outcomes after gene therapy for adenosine deaminase severe combined immune deficiencyPublished in Blood on Thursday, October 14, 2021
- Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase DeficiencyPublished in The New England Journal of Medicine on Tuesday, May 11, 2021
- Antiviral Drug Screen Identifies DNA-Damage Response Inhibitor as Potent Blocker of SARS-CoV-2 ReplicationPublished in Cell Reports on Thursday, March 18, 2021
- Lentiviral gene therapy for X-linked chronic granulomatous diseasePublished in Nature Medicine on Monday, January 27, 2020
- Lentiviral Gene Therapy in HSCs Restores Lineage-Specific Foxp3 Expression and Suppresses Autoimmunity in a Mouse Model of IPEX SyndromePublished in Cell Stem Cell on Thursday, January 10, 2019
- Improving gene therapy efficiency through the enrichment of human hematopoietic stem cellsPublished in Molecular Therapy on Tuesday, June 27, 2017
- Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoidsPublished in Nature Methods on Monday, April 3, 2017
- Clinical efficacy of gene-modified stem cells in adenosine deaminase–deficient immunodeficiencyPublished in The Journal of Clinical Investigation on Monday, March 27, 2017
- Propagating Humanized BLT Mice for the Study of Human Immunology and ImmunotherapyPublished in Stem Cells and Development on Thursday, December 15, 2016
- CRISPR/Cas9-mediated correction of the sickle mutation in human hematopoietic stem/progenitor cells Published in Molecular Therapy on Friday, July 29, 2016
- A Single CRISPR-Cas9 Deletion Strategy that Targets the Majority of DMD Patients Restores Dystrophin Function in hiPSC-Derived Muscle CellsPublished in Cell Stem Cell on Thursday, February 11, 2016
- Correction of the sickle-cell disease mutation in human hematopoietic stem/progenitor cellsPublished in Blood on Monday, March 2, 2015
- Potentially therapeutic levels of anti-sickling globin gene expression following lentivirus-mediated gene transfer in sickle cell disease bone marrow CD34+ cells Published in Experimental Hematology on Thursday, February 12, 2015
- A Modified γ-Retrovirus Vector for X-Linked Severe Combined ImmunodeficiencyPublished in The New England Journal of Medicine on Thursday, October 9, 2014
- T-Cell Immunotherapy: Looking ForwardPublished in Molecular Therapy on Wednesday, September 10, 2014
- Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United StatesPublished in Journal of the American Medical Association on Wednesday, August 20, 2014
- Transplantation Outcomes for Severe Combined Immunodeficiency, 2000–2009Published in The New England Journal of Medicine on Thursday, July 31, 2014
- HSV-sr39TK Positron Emission Tomography and Suicide Gene Elimination of Human Hematopoietic Stem Cells and Their Progeny in Humanized MicePublished in Cancer Research on Friday, July 18, 2014
- Effects of Vector Backbone and Pseudotype on Lentiviral Vector-mediated Gene Transfer: Studies in Infant ADA-Deficient Mice and Rhesus MonkeysPublished in Molecular Therapy on Friday, June 13, 2014
- Erythropoiesis from Human Embryonic Stem Cells Through Erythropoietin-Independent AKT SignalingPublished in Stem Cells on Friday, May 23, 2014
- Human Lymphoid Development in the Absence of Common γ-Chain Receptor SignalingPublished in The Journal of Immunology on Friday, April 25, 2014
- Adoptive Transfer of MART-1 T-Cell Receptor Transgenic Lymphocytes and Dendritic Cell Vaccination in Patients with Metastatic MelanomaPublished in Clinical Cancer Research on Friday, March 14, 2014
- Dissecting the Mechanism of Histone Deacetylase Inhibitors to Enhance the Activity of Zinc Finger Nucleases Delivered by Integrase-Defective Lentiviral VectorsPublished in Human Gene Therapy on Tuesday, February 25, 2014
- β-globin gene transfer to human bone marrow for sickle cell diseasePublished in Journal of Clinical Investigation on Monday, July 1, 2013
- Allelic Exclusion and Peripheral Reconstitution by TCR Transgenic T Cells Arising From Transduced Human Hematopoietic Stem/Progenitor CellsPublished in Molecular Therapy on Tuesday, February 5, 2013
- Long-term in vivo monitoring of mouse and human hematopoietic stem cell engraftment with a human positron emission tomography reporter genePublished in PNAS on Monday, January 14, 2013
- Gene therapy for adenosine deaminase–deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plansPublished in Blood Journal on Tuesday, September 11, 2012
- From skin biopsy to neurons through a pluripotent intermediate under good manufacturing practice protocolsPublished in Stem Cells Translational Medicine on Wednesday, December 7, 2011
- Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cellsPublished in PNAS on Monday, November 28, 2011
- Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivoPublished in Nature Biotechnonlogy on Friday, July 2, 2010
- Regulated Expansion of Human Pancreatic β-CellsPublished in Molecular Therapy on Tuesday, April 13, 2010
Honors & Affiliations
Honors
- Doris Duke Charitable Foundation Distinguished Clinical Scientist Award Recipient, 2000-2007
- Elizabeth Glaser Scientist Award from the Pediatric AIDS Foundation, 1996-2001
Affiliations
- President, Clinical Immunology Society, 2014
- President, American Society of Gene and Cell Therapy, 2004
- American Society for Gene and Cell Therapy
- American Society of Hematology
- American Society for Blood and Marrow Transplantation
- Jonsson Comprehensive Cancer Center Tumor Immunology Program
Funding
Kohn’s work is funded by the California Institute for Regenerative Medicine, the National Institutes of Health, and the UCLA Broad Stem Cell Research Center, including support from the Hina Patel Foundation.
Videos
Clinical Trials
- Stem Cell Gene Therapy for Sickle Cell Disease
- Autologous Transplantation of Bone Marrow CD34+ Stem/Progenitor Cells After Addition of a Normal Human ADA cDNA by the EFS-ADA Lentiviral Vector for Adenosine Deaminase (ADA)-Deficient Severe Combined Immunodeficiency (SCID)
- A Phase I/II, Non Randomized, Multicenter, Open-Label Study of G1XCGD (Lentiviral Vector Transduced CD34+ Cells) in Patients With X-Linked Chronic Granulomatous Disease
- Clinical Research Study of Autologous Stem Cell Transplantation for Sickle Cell Disease (SCD) Using Peripheral Blood CD34+ Cells Modified With the Lenti/G-βAS3-FB Lentiviral Vector
- Efficacy and Safety of Cryopreserved Formulation of Autologous CD34+ Hematopoietic Stem Cells Transduced Ex Vivo With EFS Lentiviral Vector Encoding for Human ADA Gene in Subjects With Severe Combined Immunodeficiency Due to ADA Deficiency