About

Donald B. Kohn is a Professor in the Department of Pharmacology at the University of California, Los Angeles. He holds multiple positions including Co-Leader of the Center for Translational Technologies, Professor of Pediatric Hematology/Oncology, Microbiology, Immunology & Molecular Genetics, and Molecular & Medical Pharmacology. He is also a member of several research centers such as the Blood and Marrow Transplant Center, the Center for Duchenne Muscular Dystrophy, the Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, the Genetics & Genomics GPB Home Area, the Immunity, Microbes & Molecular Pathogenesis GPB Home Area, the Molecular Pharmacology GPB Home Area, the Pilot and Collaborative Translational Clinical Studies Program, and the Tumor Immunology Program at the Jonsson Comprehensive Cancer Center (JCCC). His research focuses on immunology, infectious disease, metabolism and cancer, neurobiology, nuclear medicine, radiochemistry, and theranostics, as part of UCLA's diverse pharmacology and biomedical research initiatives.

Research topics

• Immunology
• Biology
• Medicine
• Virology
• Internal medicine
• Cell biology
• Bioinformatics
• Pharmacology
• Genetics
• Cancer research
• Oncology
• Gastroenterology

Selected publications

• Autologous Ex Vivo Lentiviral Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I Provides Sustained Efficacy with a Favorable Safety Profile

  Journal of Human Immunity · 2026-05-01

  articleOpen accessSenior author

  Background Severe leukocyte adhesion deficiency-I (LAD-I) results from biallelic deleterious ITGB2 variants leading to deficient/defective CD18 leukocyte expression and impaired endothelial adhesion and extravasation. Children with <2% of normal CD18 neutrophil expression experience recurrent, life-threatening bacterial and fungal infections, and extensive mortality. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is potentially curative but limited by donor availability, graft-versus-host disease (GvHD), and graft failure (GF). Aims To evaluate the long-term safety and efficacy of RP-L201 (marnetegragene autotemcel), an autologous CD34+ hematopoietic stem cell gene therapy utilizing the Chim-CD18-WPRE lentiviral vector carrying ITGB2, including restoration of peripheral blood (PB) polymorphonuclear cell (PMN) CD18 and CD11 expression. Methods Patients ≥3 months old with severe LAD-I enrolled in the pivotal phase I/II study (NCT03812263), underwent G-CSF/plerixafor mobilization, apheresis, ex vivo transduction of CD34+ cells with RP-L201, and myeloablative busulfan (cAUC 71.6mg/L*h) conditioning, including therapeutic drug monitoring prior to infusion. Assessments included alloHSCT-free survival, PB PMN CD18 expression, PB vector copy number (VCN) and integration site analysis (ISA), leukocytosis normalization, and infection-related hospitalization annualized events. All patients subsequently entered the long-term follow-up (LTFU) study (NCT06282432). Results As of June 18, 2025, nine patients (age at infusion 9.8–117.4 months) were treated and followed for a median (range) of 50.92 (42.6–67.9) months. AlloHSCT-free survival is 100% with no GF. VCN was 0.42–2.4 at 3 months post-infusion and remained durable thereafter with a mean VCN of 1.73 at M12, sustained through M24 and beyond with concomitant sustained PMN CD18 expression. There were no new skin or oral lesions from the end of the parent study to the data-cut date in the LTFU study. Significant infections (either requiring IV antimicrobials or hospitalization) were markedly (90.7%) reduced from pre-infusion through the following 91 days post-engraftment up to the end of the study. RP-L201 was well-tolerated with no discontinuations or RP-L201-related adverse events. ISA demonstrated highly polyclonal integration patterns without evidence of predominant clones. Summary/Conclusion Treatment with RP-L201 results in durable phenotypic correction across all relevant clinical and laboratory parameters of severe LAD-I patients. The long-term benefit-risk profile for RP-L201 remains favorable, with no RP-L201-related adverse events and 100% alloHSCT-free survival.

  PublisherDOI

• Lipid Nanoparticles for the Delivery of CRISPR/Cas9 Machinery to Enable Site‐Specific Integration of CFTR and Mutation‐Agnostic Disease Rescue (Adv. Funct. Mater. 36/2026)

  Advanced Functional Materials · 2026-05-01

  article

  Lipid Nanoparticles In their Research Article (10.1002/adfm.202502540), Steven J. Jonas and co-workers present a lipid nanoparticle (LNP) platform capable of delivering CRISPR/Cas9 machinery configured to achieve site-specific genomic integration of a full length copy of the CFTR gene at its endogenous locus, enabling rescue of the cystic fibrosis disease phenotype. The cover image illustrates LNPs being packaged with gene editing reagents, including mRNA encoding the Cas9 protein, guide RNA, and linear double stranded DNA donor templates used for this mutation agnostic gene correction strategy. The resulting nanoparticles offer a modular platform for the non-viral correction of inherited diseases.

  PublisherDOI

• HLA-Mismatched Related and Unrelated HCT Are Feasible Options for Patients with CGD without Matched Donors: A Primary Immune Deficiency Treatment Consortium Report

  Transplantation and Cellular Therapy · 2026-02-01

  article
  PublisherDOI

• Lipid Nanoparticles for the Delivery of CRISPR/Cas9 Machinery to Enable Site‐Specific Integration of CFTR and Mutation‐Agnostic Disease Rescue

  Advanced Functional Materials · 2026-01-04

  articleOpen access

  ABSTRACT We report the engineering of lipid nanoparticles (LNPs) to transport CRISPR/Cas9 payloads, including linear double‐stranded DNA (ldsDNA) donor templates, designed for homology‐directed repair (HDR)‐mediated site‐specific insertion of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene to correct cystic fibrosis (CF) in diseased airway epithelium. We screened various nanoparticle formulations, adjusting ratios of Cas9‐encoding mRNA, single guide RNAs (sgRNAs), and ldsDNA donor templates to optimize gene editing using human bronchial epithelial cells (16HBE14o‐) harboring a CF‐causing mutation (G542X). Populations of G542X cells edited via LNP delivery of CFTR donors achieved 3%–3.5% gene integration and yielded comparable CFTR protein expression compared to normal 16HBE14o‐ controls. These edited populations exhibit restoration of CFTR‐dependent Cl − current to ca. 80% of values measured in normal 16HBE14o‐ cell monolayers. This LNP platform adds capabilities for transporting large gene editing machinery to airway epithelial cells for genomic integration of entire genes, enabling therapeutic solutions that achieve correction of any CF‐causing mutation.

  PublisherOA PDFDOI

• A blueprint to accelerate rare pediatric gene therapy approvals

  Nature Medicine · 2026-03-25

  articleSenior author
  PublisherDOI

• Clinical Outcomes of Lentiviral Vector Gene Therapy for Sickle Cell Disease

  Blood Advances · 2026-04-20

  articleOpen accessSenior author

  Sickle cell disease (SCD) is a monogenic disorder where autologous gene therapy may offer a safer curative alternative to allogeneic transplantation. We report outcomes from a Phase I/II study using the Lenti/G-βAS3-FB lentiviral vector, encoding an anti-sickling β-globin. This trial was registered at ClinicalTrials.gov (NCT02247843). This single-site study treated four adults with severe SCD. The first patient was treated using the original Lenti/βAS3-FB and initial protocol, which resulted in suboptimal clinical response. Subsequent protocol refinements included improved hematopoietic stem and progenitor cell (HSPC) collection using plerixafor-mobilized peripheral blood apheresis with pre-collection erythrocytapheresis, and use of an optimized lentiviral vector with a transduction enhancer. All patients received myeloablative busulfan conditioning followed by infusion of gene-modified autologous HSPCs. Primary endpoints were safety and feasibility; secondary endpoints included gene marking, therapeutic hemoglobin expression, and clinical outcomes. All patients achieved hematopoietic recovery without rescue transplantation. The first patient demonstrated low gene marking (peak vector copy number [VCN] 0.035) and undetectable HbAS3 expression, with minimal clinical benefit. In contrast, the three patients treated with the optimized protocol achieved higher and sustained gene marking (peak granulocyte VCNs ~0.5-2.0) and persistent HbAS3 expression. These patients experienced some reductions in vaso-occlusive crises and transfusion requirements, with two becoming transfusion-independent. No insertional oncogenesis was observed. This trial highlights the necessity of optimized vector design and transduction protocols to achieve durable gene expression. While this specific vector will not be pursued further, the study provides crucial insights into gene therapy protocol development.

  PublisherDOI

• Investigation of Double-Stranded DNA Donors and CRISPR-Cas9 RNP for Universal Correction of Mutations Causing Cystic Fibrosis in Human Airway Cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-21

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Cystic fibrosis (CF) is a devastating genetic disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator ( CFTR ) gene. As morbidity and mortality from CF results from a lack of mucus clearance that leads to chronic bacterial infections and progressive loss of lung function, site-specific insertion of a CFTR cDNA into the endogenous CFTR locus in airway basal stem cells (ABSCs) could prove curative for all disease-causing mutations. This study describes the development of nonviral genome editing reagents, designed to be packaged into nonviral delivery systems. An sgRNA targeting the 5’ untranslated region of CFTR was characterized as directing high on-target cutting and displaying a safe off-target profile. Airway cell lines electroporated with chemically-modified (1-Aminohexane - AmC6), linear double-stranded DNA (ldsDNA) constructs were utilized as an Homology Directed Repair (HDR) donor, initially optimized with an mCitrine reporter. Expectedly, when the 780bp mCitrine cDNA was replaced with the 4.4kb CFTR cDNA, integration efficiency dropped significantly. However, 1-2% integration of codon optimized donors was sufficient to restore CFTR expression in the bulk edited population of human bronchial epithelial cell line, 16HBE14o- (16HBE), to levels reaching 50% of wildtype expression as measured by Western Blot. Electrophysiological validation of CFTR ion channel function measured via Ussing Chamber Assay revealed that these bulk edited populations exhibit greater than 40% restoration of the chloride ion currents of the measured wildtype controls. These results demonstrate that low levels of CFTR integration can be made therapeutically relevant by optimizing the designs of gene editing reagents. Importantly, this work utilizes nonviral editing reagents, an essential step towards in vivo gene therapy for CF.

  PublisherOA PDFDOI

• Hematopoietic stem cell gene therapy for the treatment of X-linked agammaglobulinemia

  Molecular Therapy — Methods & Clinical Development · 2025-08-12 · 2 citations

  articleOpen accessSenior author

  cDNA transgene directly into its endogenous locus. To study the effectiveness of this therapy, murine lineage-negative hematopoietic cells from a murine model of XLA were edited using CRISPR-Cas9/rAAV6 then transplanted into recipient XLA mice. Myeloablated XLA mice that received transplantation of Btk-corrected Lin- cells displayed high levels of engraftment, significant increases in their B cell levels, increased production of various immunoglobulins, improved B cell development in the bone marrow, increased B cell receptor diversity, and the ability to produce antigen-specific antibodies following immunization. Collectively, we have modeled a gene therapy strategy in a disease model of XLA and extensively validated the site-specific genome editing approach.

  PublisherDOI

• Oligonucleotide synthesis errors are a source of untoward variation in HDR-mediated gene editing

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-11 · 1 citations

  preprintOpen access

  Abstract Single-stranded oligonucleotides (ssODNs) are used as donor templates for therapeutic gene editing by CRISPR-Cas9 cleavage and homology-directed repair (HDR). Although ssODN sequence fidelity is critical to the safety and efficacy of editing, standard quality control methods cannot resolve individual nucleotide errors. By deep sequencing ssODNs from three manufacturers, and amplicons from edited hematopoietic stem/progenitor cells, we find that synthesis errors are present in all ssODNs tested at rates that vary more than two-fold among manufacturers, at positions that are dependent on sequence context. These synthesis errors are propagated into the genome by HDR at frequencies proportional to their abundance in the ssODN. In our sickle cell mutation correction protocol, the most prevalent SNEs are predicted to produce benign β-globin variants, while the less frequent frameshift deletions will generate β-thalassemia alleles. Current quality control standards are insufficient to detect these errors, and deep sequencing of ssODNs should be incorporated into regulatory submissions for clinical gene editing programs.

  PublisherOA PDFDOI

• Outcomes following matched sibling donor transplantation for severe combined immunodeficiency: a report from the PIDTC

  Blood Advances · 2025-11-25

  articleOpen access

  ABSTRACT: The Primary Immune Deficiency Treatment Consortium performed a retrospective analysis of 133 patients with severe combined immunodeficiency (SCID) receiving matched sibling donor (MSD) hematopoietic cell transplantation (HCT) between 1980 and 2023 at 30 North American institutions. In this largest cohort of MSD outcomes in patients with SCID to date, we examined the impact of conditioning regimen and graft-versus-host disease (GVHD) prophylaxis on survival and immune recovery. Outcomes after MSD HCT for SCID were excellent. Patients without an active infection or failure to thrive (FTT) at the time of HCT had 5-year overall survival superior to those with infection or FTT. Acute and chronic GVHD outcomes were independent of GVHD prophylaxis, conditioning regimen, SCID type, or presence of maternal engraftment. Patients without active infection at the time of HCT had superior chronic GVHD-free event-free survival vs those with infection. T-cell reconstitution at 6 months was less likely achieved with use of GVHD prophylaxis or serotherapy, and in patients with leaky SCID or Omenn syndrome. At 6 months, 1 year, and 2-5 years, T-cell reconstitution was less likely with ADA, DCLRE1C, or RAG genotype. B-cell reconstitution at 1 year and 2-5 years was negatively affected by development of grade 2 to 4 or 3 to 4 acute GVHD. Conditioning did not affect T- or B-cell reconstitution. Our data suggest omitting conditioning and GVHD prophylaxis for patients with typical SCID did not negatively affect 5-year outcomes after MSD HCT, but the data are insufficient to recommend this approach for best long-term outcomes. This trial was registered at www.clinicaltrials.gov as #NCT01186913 and #NCT01346150.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01DK048700

  NIH · $194k · 1998

• Tissue Engineering and Regeneration

  NIH · $18.1M · 1976–2027

• NIH Grant R01AI074043

  NIH · $2.3M · 2013

• Severe Combined Immune Deficiency: Prospective and Longitudinal Study of Genotypes, Management and Outcomes

  NIH · $45.2M · 2009–2025

• NIH Grant R01AI052798

  NIH · $1.8M · 2007

Frequent coauthors

• Roger P. Hollis

  University of California, Los Angeles

  175 shared

• Gay M. Crooks

  University of California, Los Angeles

  131 shared

• Antoni Ribas

  Parker Institute for Cancer Immunotherapy

  105 shared

• Owen N. Witte

  102 shared

• Kenneth Cornetta

  AMPATH

  102 shared

• Luigi D. Notarangelo

  National Institute of Allergy and Infectious Diseases

  96 shared

• Sung‐Yun Pai

  Center for Cancer Research

  90 shared

• Kenneth I. Weinberg

  Stanford University

  88 shared

Education

• M.D., School of Medicine

  University of Wisconsin Madison

  1982

• M.S., Microbiology

  University of Illinois at Urbana-Champaign

  1978

• B.S., Biology

  University of Illinois at Urbana-Champaign

  1976