Donald B. Kohn
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View article: Outcomes Following Hematopoietic Cell Transplant in CD3δ SCID Patients in Canada
Outcomes Following Hematopoietic Cell Transplant in CD3δ SCID Patients in Canada Open
Introduction In the Low German Mennonite (LGM) population, CD3δ severe combined immunodeficiency (SCID) is the result of a homozygous c.202C>T; p.Arg68Ter pathogenic variant. The block in T cell development causes infant mortality witho…
View article: Outcomes Following Matched Sibling Donor Transplantation for Severe Combined Immunodeficiency: A Report from the PIDTC
Outcomes Following Matched Sibling Donor Transplantation for Severe Combined Immunodeficiency: A Report from the PIDTC Open
The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 133 patients with severe combined immunodeficiency (SCID) receiving matched sibling donor (MSD) hematopoietic cell transplantation (HCT) between…
View article: Neurodevelopmental outcomes following hematopoietic cell transplantation for patients with severe combined immunodeficiency (SCID): A PIDTC study
Neurodevelopmental outcomes following hematopoietic cell transplantation for patients with severe combined immunodeficiency (SCID): A PIDTC study Open
Hematopoietic cell transplantation (HCT) is a potentially curative treatment for severe combined immunodeficiency (SCID). Since the initiation of newborn screening (NBS), survival rates have improved significantly, but the impact of HCT up…
View article: Synthetic oligonucleotides contain synthesis errors that are propagated into the genome by editing through homology-directed repair
Synthetic oligonucleotides contain synthesis errors that are propagated into the genome by editing through homology-directed repair Open
Single-stranded oligonucleotides (ssODNs) serve as donor templates for gene editing through targeted endonuclease cleavage and homology-directed repair (HDR). While oligonucleotide synthesis is a mature technology, the quality of products …
View article: Investigation of Double-Stranded DNA Donors and CRISPR-Cas9 RNP for Universal Correction of Mutations Causing Cystic Fibrosis in Human Airway Cells
Investigation of Double-Stranded DNA Donors and CRISPR-Cas9 RNP for Universal Correction of Mutations Causing Cystic Fibrosis in Human Airway Cells Open
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 chr…
View article: Lentiviral vectors for hematopoietic stem cell gene therapy restore α-globin expression in α-thalassemia red blood cells
Lentiviral vectors for hematopoietic stem cell gene therapy restore α-globin expression in α-thalassemia red blood cells Open
Alpha thalassemia major (ATM) is an inherited blood disorder caused by the absence of all four α-globin genes (HBA2/1), resulting in severe anemia and lifelong transfusion dependence. While allogeneic hematopoietic stem cell transplantatio…
View article: Synthesis errors in oligonucleotides are propagated into the genome by homology-directed repair
Synthesis errors in oligonucleotides are propagated into the genome by homology-directed repair Open
Single-stranded oligonucleotides (ssODNs) are used as donor templates for gene editing by targeted endonuclease cleavage and homology directed repair (HDR). We probed their sequence fidelity by deep sequencing ssODNs from three manufacture…
View article: Quantifying the mutational landscape of retroviral and lentiviral vectors in gene therapy patients
Quantifying the mutational landscape of retroviral and lentiviral vectors in gene therapy patients Open
Adenosine deaminase severe combined immunodeficiency (ADA-SCID) is a monogenic disorder caused by mutations in the ADA gene. Gene therapy using γ-retroviral and lentiviral vector gene addition approaches have shown curative results. We seq…
View article: Post-Transplant Chronic Granulomatous Disease Patient Follow-Up: A PIDTC Survey
Post-Transplant Chronic Granulomatous Disease Patient Follow-Up: A PIDTC Survey Open
Background Chronic granulomatous disease (CGD) is an inborn error of immunity caused by defects in NADPH oxidase, which causes phagocyte dysfunction. CGD is characterized by recurrent infections and autoimmunity. Allogeneic hematopoietic s…
View article: Determining the Genetic Drivers of Diffuse Large B Cell Lymphoma 30 Years After Gamma Retroviral Gene Therapy for Severe Combined Immunodeficiency due to Adenosine Deaminase Deficiency
Determining the Genetic Drivers of Diffuse Large B Cell Lymphoma 30 Years After Gamma Retroviral Gene Therapy for Severe Combined Immunodeficiency due to Adenosine Deaminase Deficiency Open
In 1993, a newborn with adenosine deaminase–deficient severe combined immunodeficiency (ADA-SCID) received investigational gene therapy with autologous cord blood cells transduced with a gammaretroviral ADA vector infused without condition…
View article: Stage-specific CAR-mediated signaling generates naïve-like, TCR-null CAR T cells from induced pluripotent stem cells
Stage-specific CAR-mediated signaling generates naïve-like, TCR-null CAR T cells from induced pluripotent stem cells Open
Genetically modified, induced pluripotent stem cells (iPSCs) offer a promising allogeneic source for the generation of functionally enhanced, chimeric antigen receptor (CAR) T cells. However, the signaling of CARs during early T cell devel…
View article: Ex Vivo Lentiviral Hematopoietic Stem Cell (HSC) Gene Therapy May Represent a Curative Therapy for the Life-Threatening Inborn Error of Immunity Severe Combined Immunodeficiency Due to Adenosine Deaminase (ADA) Deficiency (ADA-SCID)
Ex Vivo Lentiviral Hematopoietic Stem Cell (HSC) Gene Therapy May Represent a Curative Therapy for the Life-Threatening Inborn Error of Immunity Severe Combined Immunodeficiency Due to Adenosine Deaminase (ADA) Deficiency (ADA-SCID) Open
Introduction: Ex Vivo Lentiviral Hematopoietic Stem Cell (HSC) Gene Therapy May Represent a Curative Therapy for the Life-Threatening Inborn Error of Immunity Severe Combined Immunodeficiency Due to Adenosine Deaminase (ADA) Deficiency (AD…
View article: DNA contamination within recombinant adeno-associated virus preparations correlates with decreased CD34+ cell clonogenic potential
DNA contamination within recombinant adeno-associated virus preparations correlates with decreased CD34+ cell clonogenic potential Open
Recombinant adeno-associated viruses (rAAV) are promising for applications in many genome editing techniques through their effectiveness as carriers of DNA homologous donors into primary hematopoietic stem and progenitor cells (HSPCs), but…
View article: Successful Gene Editing of Apolipoprotein E4 to E3 in Brain of Alzheimer Model Mice After a Single IV Dose of Synthetic Exosome-Delivered CRISPR
Successful Gene Editing of Apolipoprotein E4 to E3 in Brain of Alzheimer Model Mice After a Single IV Dose of Synthetic Exosome-Delivered CRISPR Open
Background The gene for apolipoprotein E4 (ApoE4 E4) confers an increased risk for development and lowers the age of onset of Alzheimer’s disease (AD), and is a highly suitable target for CRISPR-based editing because ApoE4 differs from Apo…
View article: What a Clinician Needs to Know About Genome Editing: Status and Opportunities for Inborn Errors of Immunity
What a Clinician Needs to Know About Genome Editing: Status and Opportunities for Inborn Errors of Immunity Open
During the past 20 years, gene editing has emerged as a novel form of gene therapy. Since the publication of the first potentially therapeutic gene editing platform for genetic disorders, increasingly sophisticated editing technologies hav…
View article: Gene therapy for adenosine deaminase severe combined immune deficiency—An unexpected journey of four decades
Gene therapy for adenosine deaminase severe combined immune deficiency—An unexpected journey of four decades Open
Summary Severe combined immune deficiency due to adenosine deaminase deficiency (ADA SCID) is an inborn error of immunity with pan‐lymphopenia, due to accumulated cytotoxic adenine metabolites. ADA SCID has been treated using gene therapy …
View article: Autologous MPO Knock-out Hematopoietic Stem and Progenitor Cells for Pulmonary Arterial Hypertension
Autologous MPO Knock-out Hematopoietic Stem and Progenitor Cells for Pulmonary Arterial Hypertension Open
Pulmonary Arterial Hypertension (PAH) is a progressive condition for which there is no cure. Even with substantial pharmacologic advances in the modern treatment era, existing treatments provide only symptomatic relief and survival remains…
View article: Busulfan and subsequent malignancy: An evidence‐based risk assessment
Busulfan and subsequent malignancy: An evidence‐based risk assessment Open
Background The incidence of secondary malignancies associated with busulfan exposure is considered low, but has been poorly characterized. Because this alkylating agent is increasingly utilized as conditioning prior to gene therapy in nonm…