Paul B. McCray

CFTR gene delivery to human airway epithelia using parainfluenza virus 5 amplifying virus-like particles

Mark A. Phillips, Lei Lei, Katarina Kulhánková, María Cristina Gingerich et autres

reporter (AVLP-CFTR). We examined the transduction efficiency and persistence of transgene expression of AVLP-eGFP in primary cultures of non-CF and CF human airway epithelia (HAE). When applied to the apical surface of HAE, the AVLP-eGFP mainly transduced ciliated epithelial cells, with lesser …

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Optimized AAV capsids robustly transduce airway epithelial cells

Ashley Cooney, Yong Hong Chen, Brian C. Lewandowski, Shakayla Lamer et autres

Gene therapies have demonstrated transformative potential for a range of genetic disorders, including immunodeficiencies, hematopoietic conditions, and neuromuscular diseases. However, the application of these approaches to cystic fibrosis (CF) and other airway diseases remains constrained by the challenge of efficient gene delivery …

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Novel mouse reporter models for the detection of genome editing events in vivo

Kathy J. Snow, Ethan Saville, Caleb Heffner, Yaned Gaitan et autres

Abstract With the expansion of therapeutic gene editing technology, small animal models provide essential platforms to evaluate the function of these new approaches in vivo . As part of the Somatic Cell Genome Editing (SCGE) Consortium, we developed next-generation murine reporters that …

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Considerations for early life genetic therapies in cystic fibrosis

Ashley L. Cooney, Ian M. Thornell, Alejandro A. Pezzulo, Anthony J. Fischer et autres

Cystic fibrosis (CF) is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) anion channel. Since the initial characterization of CF in the early 20th century, advances in clinical management have reduced disease burden and increased longevity. …

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Lentiviral-mediated gene complementation to rescue pathogenic ABCA3 variants

Ashley L. Cooney, Shakayla Lamer, Ping Yang, Daniel J Wegner et autres

The ATP-binding cassette subfamily A member 3 (ABCA3) protein in the limiting membrane of lamellar bodies in alveolar type 2 (AT2) cells transports phospholipids required for pulmonary surfactant assembly. ABCA3 deficiency results from biallelic pathogenic variants in ABCA3 and causes progressive neonatal …

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In Utero CFTR Modulation Alleviates Disease in G551D Cystic Fibrosis Pigs

Sarah E. Ernst, David Kyle Meyerholz, Melissa Shaelyn Samuel, Kristin M. Whitworth et autres

ABSTRACT Previous studies indicate that pigs with CFTR-null and CFTR-ΔF508 mutations develop multiorgan disease similar to that in people with cystic fibrosis (CF). At birth, their airways exhibit host defense defects that predispose to airway infection, inflammation, and mucus accumulation. The CFTR-G551D …

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219 Peptide insertions enhance AAV capsid tropism for airway epithelia

Ashley L. Cooney, Yan Chen, Bogumił Lewandowski, Shakayla Lamer et autres

IL-13 decreases susceptibility to airway epithelial SARS-CoV-2 infection but increases disease severity in vivo via eicosanoid signalling

Shreya Ghimire, Biyun Xue, Kun Li, Ryan M. Gannon et autres

Background Treatments available to prevent progression of virus-induced lung diseases, including coronavirus disease 2019 (COVID-19) are of limited benefit once respiratory failure occurs. The efficacy of approved and emerging cytokine signalling-modulating antibodies is variable and is affected by disease course and patient-specific …

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Lentiviral-mediated gene complementation rescues pathogenic ABCA3 variants

Ashley L. Cooney, Shakayla Lamer, Ping Yang, Frances V. White et autres

ABSTRACT The ATP-binding cassette subfamily A member 3 (ABCA3) protein on the limiting membrane of lamellar bodies in alveolar type 2 (AT2) cells transports phospholipids required for pulmonary surfactant assembly. ABCA3 deficiency results from biallelic pathogenic variants in ABCA3 and causes progressive …

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Complement expression determines disease severity in mouse models of SARS-CoV-2 and influenza pneumonia

Peter Szachowicz, Alexander J. Watson, Christine Wohlford-Lenane, Boopathi Sownthirarajan et autres

The role of complement in the host response to respiratory viral infections is debated, with evidence suggesting it can either promote an effective immune response, or induce excessive inflammation and acute lung injury. During the COVID-19 pandemic, complement was implicated in disease …

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Role of COPA Gene Mutation in Lung Epithelial Cells in COPA Syndrome Lung Disease

Kazuya Koyama, C. Koziol, Alejandro A. Pezzulo, Scott H. Randell et autres

Abstract Rationale: COPA syndrome is an autosomal dominant systemic inflammatory disease, which includes interstitial lung disease (ILD) as a major clinical feature. This syndrome is caused by mutations in the COPA gene, leading to dysfunction in the coatomer protein complex I subunit …

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CF airway epithelia display exaggerated host defense responses and prolonged cilia loss during RSV infection

Jennifer A. Bartlett, Eric D. Huntemann, Sateesh Krishnamurthy, Stacey M. Hartwig et autres

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