Abstract 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 manufacturers, and genomes derived from editing using these ssODNs as templates for HDR. The ssODNs carry single-nucleotide and small deletion synthesis errors in proportions differing widely among manufacturers; these are propagated into the genome by HDR; therapeutic gene correct…

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 sequenced the ADA transgene in transduced CD3⁺ T cells, and in peripheral blood cells from patients treated with autologous CD34⁺ cells transduced with either a γ-retroviral or lentiviral ADA gene vector to assess transgene mutational profiles. In both CD3<sup>…

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 stem cell transplantation (HSCT) is a curative therapy. However, data regarding patient satisfaction with post-HSCT state of health and quality of life are lacking. Methods A Primary Immune Deficiency Treatment Consortium (PIDTC) working group designed online surveys to assess pos…

Introduction In the Low German Mennonite (LGM) population, CD3δ severe combined immunodeficiency (SCID) is the result of a homozygous c.202C&amp;gt;T; p.Arg68Ter pathogenic variant. The block in T cell development causes infant mortality without allogeneic hematopoietic cell transplantation (HCT). We evaluated outcomes following HCT in Canadian LGM infants from 2011-2023. Methods Data were collected and analyzed using descriptive statistics for 11 patients treated in Alberta and Manitoba in collaboration with the …

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 nonvi…