Dr. Donald Kohn is a Professor in the Departments of Microbiology, Immunology & Molecular Genetics (M.I.M.G.) and Pediatrics and is the Director of the Human Gene Medicine Program. He served as an attending physician in the pediatric bone marrow transplant program at Childrens Hospital Los Angeles for more than 20 years. His research focuses on the development of new methods to treated genetic diseases of blood cells and cancer and leukemia by gene modification of hematopoietic stem cells. Kohn’s group was the first (and still the only one) to perform a clinical trial with gene transfer to umbilical cord blood CD34+ cells for a genetic disorder (ADA-SCID in 1993) and the first in the U.S. to initiate a clinical trial of gene therapy for pediatric AIDS using bone marrow stem cells.
Kohn's laboratory is currently focused on two main areas: 1) the development and clinical evaluation of improved methods for gene therapy of genetic diseases of blood cells targeting hematopoietic stem cells, especially ADA-deficient SCID and sickle cell disease, and 2) immunotherapy for cancer and leukemia by genetic modification of hematopoietic stem cells to produce targeted effector cells. Pre-clinical studies are focused on the use of lentiviral vectors for gene addition to stem cells and zinc-finger nucleases for gene correction by homologous recombination. His lab is currently performing a clinical trial of retroviral vector-mediated ADA gene transfer for children with ADA-deficient SCID and is working toward trials using lentiviral vectors for ADA-deficient SCID and sickle cell disease. In addition, Kohn’s group is participating as one of three U.S. sites for an NIAID-funded clinical trial of gene therapy for X-SCID.
Selected Cancer-Related Publications:
Tarantal AF, Giannoni F, Sumiyoshi T, Lee CI, Hollis RH, Wherley J, Martinez M, Leapley A, Kahl C, Louie SG, Kohn DB. Non-Myeloablative Conditioning Regimen to Increase Engraftment of Gene-Modified Hematopoietic Stem Cells. Mol Ther 2012 Jan 31. [Epub ahead of print]
Vatakis DN, Koya RC, Nixon CC, Wei L, Kim SG, Avancena P, Bristol G, Baltimore D, Kohn DB, Ribas A, Radu CG, Galic Z, Zack JA. Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cells. Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):E1408-16. Epub 2011 Nov 28.
Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, Crooks GM, Kohn DB, Gregory PD, Holmes MC, Cannon PM. Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat Biotechnol. 2010 Aug;28(8):839-47. Epub 2010 Jul 2.
Kohn DB, Candotti F. Gene therapy fulfilling its promise. N Engl J Med. 2009 Jan 29;360(5):518-21.
Carbonaro DA, Jin X, Cotoi D, Mi T, Yu XJ, Skelton DC, Dorey F, Kellems RE, Blackburn MR, Kohn DB. Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion. Blood. 2008 Jun 15;111(12):5745-54. Epub 2008 Mar 20.