Emerging gene therapies for cystic fibrosis

Novel chimeric gene therapy vectors based on Adeno-associated virus (AAV) and four different mammalian bocaviruses (BoV)

(2019) Julia Fakhiri et al.   Molecular Therapy-Methods & Clinical Development

In utero and postnatal VX-770 administration rescues multiorgan disease in a ferret model of cystic fibrosis

(2019) Xingshen Sun et al.   Science Translational Medicine

Self-assembled peptide–poloxamine nanoparticles enable in vitro and in vivo genome restoration for cystic fibrosis

(2019) Shan Guan et al.   Nature Nanotechnology

Identification of preexisting adaptive immunity to Cas9 proteins in humans

(2019) Carsten T. Charlesworth et al.   NATURE MEDICINE

Staphylococcus aureus in the airways of cystic fibrosis patients - A retrospective long-term study

(2018) Mathias Schwerdt et al.   INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY

R560S: A class II CFTR mutation that is not rescued by current modulators

(2018) Nikhil T. Awatade et al.   Journal of Cystic Fibrosis

Lipid Nanoparticle-Delivered Chemically Modified mRNA Restores Chloride Secretion in Cystic Fibrosis

(2018) Ema Robinson et al.   MOLECULAR THERAPY

Bioengineered AAV Capsids with Combined High Human Liver Transduction In Vivo and Unique Humoral Seroreactivity

(2018) Nicole K. Paulk et al.   MOLECULAR THERAPY

Effective silencing of ENaC by siRNA delivered with epithelial-targeted nanocomplexes in human cystic fibrosis cells and in mouse lung

(2018) Aristides D Tagalakis et al.   THORAX

Evaluation of autophagy inducers in epithelial cells carrying the ΔF508 mutation of the cystic fibrosis transmembrane conductance regulator CFTR

(2018) Shaoyi Zhang et al.   Cell Death & Disease

Biopolymer-Based Nanoparticles for Cystic Fibrosis Lung Gene Therapy Studies

(2018) Elena Fernández Fernández et al.   Materials

Epithelial disruption: a new paradigm enabling human airway stem cell transplantation

(2018) Nigel Farrow et al.   Stem Cell Research & Therapy

An Adeno-Associated Viral Vector Capable of Penetrating the Mucus Barrier to Inhaled Gene Therapy

(2018) Gregg A. Duncan et al.   Molecular Therapy-Methods & Clinical Development

A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte

(2018) Lindsey W. Plasschaert et al.   NATURE

Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor

(2018) William J. Zacharias et al.   NATURE

A revised airway epithelial hierarchy includes CFTR-expressing ionocytes

(2018) Daniel T. Montoro et al.   NATURE

Widespread airway distribution and short-term phenotypic correction of cystic fibrosis pigs following aerosol delivery of piggyBac/adenovirus

(2018) Ashley L Cooney et al.   NUCLEIC ACIDS RESEARCH

A novel triple combination of pharmacological chaperones improves F508del-CFTR correction

(2018) Graeme W. Carlile et al.   Scientific Reports

Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein

(2018) Trine Dalsgaard et al.   Molecular Therapy-Nucleic Acids

An Observational Study from Long-Term AAV Re-administration in Two Hemophilia Dogs

(2018) Junjiang Sun et al.   Molecular Therapy-Methods & Clinical Development

Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis

(2018) Isabelle Sermet-Gaudelus et al.   Journal of Cystic Fibrosis

VX-445–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles

(2018) Dominic Keating et al.   NEW ENGLAND JOURNAL OF MEDICINE

VX-659–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles

(2018) Jane C. Davies et al.   NEW ENGLAND JOURNAL OF MEDICINE

Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

(2018) Amine Meliani et al.   Nature Communications

Chemically modified hCFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis

(2018) A. K. M. Ashiqul Haque et al.   Scientific Reports

Cell Therapy for Cystic Fibrosis Lung Disease: Regenerative Basal Cell Amplification

(2018) Don Hayes et al.   Stem Cells Translational Medicine

Gene therapy for Cystic Fibrosis: Improved delivery techniques and conditioning with lysophosphatidylcholine enhance lentiviral gene transfer in mouse lung airways

(2017) Patricia Cmielewski et al.   EXPERIMENTAL LUNG RESEARCH

Novel GP64 envelope variants for improved delivery to human airway epithelial cells

(2017) P L Sinn et al.   GENE THERAPY

Human Bocavirus Type-1 Capsid Facilitates the Transduction of Ferret Airways by Adeno-Associated Virus Genomes

(2017) Ziying Yan et al.   HUMAN GENE THERAPY

CRISPR/Cas9-mediated somatic and germline gene correction to restore hemostasis in hemophilia B mice

(2017) Cong Huai et al.   HUMAN GENETICS

Data Resource Profile: The UK Cystic Fibrosis Registry

(2017) David Taylor-Robinson et al.   INTERNATIONAL JOURNAL OF EPIDEMIOLOGY

Human Bocavirus 1 Is a Novel Helper for Adeno-associated Virus Replication

(2017) Zekun Wang et al.   JOURNAL OF VIROLOGY

Exosome-associated AAV2 vector mediates robust gene delivery into the murine retina upon intravitreal injection

(2017) Sarah J. Wassmer et al.   Scientific Reports

Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway

(2017) Clare E. Weeden et al.   PLOS BIOLOGY

Cas9/gRNA targeted excision of cystic fibrosis-causing deep-intronic splicing mutations restores normal splicing of CFTR mRNA

(2017) David J. Sanz et al.   PLoS One

Delivery of ENaC siRNA to epithelial cells mediated by a targeted nanocomplex: a therapeutic strategy for cystic fibrosis

(2017) Maria D. I. Manunta et al.   Scientific Reports

rAAV-CFTRΔR Rescues the Cystic Fibrosis Phenotype in Human Intestinal Organoids and Cystic Fibrosis Mice

(2016) Dragana Vidović et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Preclinical evaluation of RNAi as a treatment for transthyretin-mediated amyloidosis

(2016) James S. Butler et al.   AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS

CRISPR/Cas9‐mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse

(2016) Yuting Guan et al.   EMBO Molecular Medicine

Exosome-associated AAV vector as a robust and convenient neuroscience tool

(2016) E Hudry et al.   GENE THERAPY

Gene Therapy for X-Linked Severe Combined Immunodeficiency: Where Do We Stand?

(2016) Marina Cavazzana et al.   HUMAN GENE THERAPY

Pulmonary Targeting of Adeno-associated Viral Vectors by Next-generation Sequencing-guided Screening of Random Capsid Displayed Peptide Libraries

(2016) Jakob Körbelin et al.   MOLECULAR THERAPY

In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration

(2016) Keiichiro Suzuki et al.   NATURE

A multifunctional AAV–CRISPR–Cas9 and its host response

(2016) Wei Leong Chew et al.   NATURE METHODS

Preparation for a first-in-man lentivirus trial in patients with cystic fibrosis

(2016) Eric W F W Alton et al.   THORAX

RNAs Containing Modified Nucleotides Fail To Trigger RIG-I Conformational Changes for Innate Immune Signaling

(2016) Ann Fiegen Durbin et al.   mBio

Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup: a pooled analysis

(2016) J Stuart Elborn et al.   Lancet Respiratory Medicine

Targeted Integration of a Super-Exon into the CFTR Locus Leads to Functional Correction of a Cystic Fibrosis Cell Line Model

(2016) Christien Bednarski et al.   PLoS One

Precision Medicine: At What Price?

(2015) Thomas Ferkol et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Evaluation of tetrafunctional block copolymers as synthetic vectors for lung gene transfer

(2015) Peggy Richard-Fiardo et al.   BIOMATERIALS

Adenovirus-Mediated Somatic Genome Editing ofPtenby CRISPR/Cas9 in Mouse Liver in Spite of Cas9-Specific Immune Responses

(2015) Dan Wang et al.   HUMAN GENE THERAPY

Correction of a Cystic Fibrosis Splicing Mutation by Antisense Oligonucleotides

(2015) Susana Igreja et al.   HUMAN MUTATION

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)

(2015) Valentina Corradi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Liver-directed lentiviral gene therapy in a dog model of hemophilia B

(2015) Alessio Cantore et al.   Science Translational Medicine

Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium

(2015) Nicole Ali McNeer et al.   Nature Communications

Functional Gene Correction for Cystic Fibrosis in Lung Epithelial Cells Generated from Patient iPSCs

(2015) Amy L. Firth et al.   Cell Reports

Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial

(2015) Eric W F W Alton et al.   Lancet Respiratory Medicine

Targeted Correction and Restored Function of the CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells

(2015) Ana M. Crane et al.   Stem Cell Reports

Rescue of NBD2 Mutants N1303K and S1235R of CFTR by Small-Molecule Correctors and Transcomplementation

(2015) Daniele Rapino et al.   PLoS One

Longevity of Patients With Cystic Fibrosis in 2000 to 2010 and Beyond: Survival Analysis of the Cystic Fibrosis Foundation Patient Registry

(2014) Todd MacKenzie et al.   ANNALS OF INTERNAL MEDICINE

Naturally enveloped AAV vectors for shielding neutralizing antibodies and robust gene delivery in vivo

(2014) Bence György et al.   BIOMATERIALS

Mystery solved: VSV-G-LVs do not allow efficient gene transfer into unstimulated T cells, B cells, and HSCs because they lack the LDL receptor

(2014) F. Amirache et al.   BLOOD

Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial

(2014) Stéphane Palfi et al.   LANCET

Overcoming the Cystic Fibrosis Sputum Barrier to Leading Adeno-associated Virus Gene Therapy Vectors

(2014) Benjamin S Schuster et al.   MOLECULAR THERAPY

Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B

(2014) Amit C. Nathwani et al.   NEW ENGLAND JOURNAL OF MEDICINE

Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis

(2014) M. J. Hoegger et al.   SCIENCE

Delivery of genes into the CF airway

(2014) Deborah R Gill et al.   THORAX

B-cell depletion is protective against anti-AAV capsid immune response: a human subject case study

(2014) M Corti et al.   Molecular Therapy-Methods & Clinical Development

Disease-relevant proteostasis regulation of cystic fibrosis transmembrane conductance regulator

(2013) V R Villella et al.   CELL DEATH AND DIFFERENTIATION

Functional Repair of CFTR by CRISPR/Cas9 in Intestinal Stem Cell Organoids of Cystic Fibrosis Patients

(2013) Gerald Schwank et al.   Cell Stem Cell

Rationale and design of a randomized trial of home electronic symptom and lung function monitoring to detect cystic fibrosis pulmonary exacerbations: The early intervention in cystic fibrosis exacerbation (eICE) trial

(2013) N. Lechtzin et al.   Contemporary Clinical Trials

Vesicular Stomatitis Virus Glycoprotein– and Venezuelan Equine Encephalitis Virus-Derived Glycoprotein–Pseudotyped Lentivirus Vectors Differentially Transduce Corneal Endothelium, Trabecular Meshwork, and Human Photoreceptors

(2013) Daniel M. Lipinski et al.   HUMAN GENE THERAPY

Transcomplementation by a Truncation Mutant of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Enhances ΔF508 Processing through a Biomolecular Interaction

(2013) Liudmila Cebotaru et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs

(2013) David A. Stoltz et al.   JOURNAL OF CLINICAL INVESTIGATION

High efficiency gene transfer to airways of mice using influenza hemagglutinin pseudotyped lentiviral vectors

(2013) Manij Patel et al.   JOURNAL OF GENE MEDICINE

Enhanced Central Nervous System Transduction with Lentiviral Vectors Pseudotyped with RVG/HIV-1gp41 Chimeric Envelope Glycoproteins

(2013) A. Trabalza et al.   JOURNAL OF VIROLOGY

A Novel Chimeric Adenoassociated Virus 2/Human Bocavirus 1 Parvovirus Vector Efficiently Transduces Human Airway Epithelia

(2013) Ziying Yan et al.   MOLECULAR THERAPY

A functional CFTR assay using primary cystic fibrosis intestinal organoids

(2013) Johanna F Dekkers et al.   NATURE MEDICINE

Preferential Lentiviral Targeting of Astrocytes in the Central Nervous System

(2013) Michael Fassler et al.   PLoS One

Mechanosensitive ATP Release Maintains Proper Mucus Hydration of Airways

(2013) B. Button et al.   Science Signaling

In Vivo-Directed Evolution of a New Adeno-Associated Virus for Therapeutic Outer Retinal Gene Delivery from the Vitreous

(2013) D. Dalkara et al.   Science Translational Medicine

Regulation of Trachebronchial Tissue-Specific Stem Cell Pool Size

(2013) Moumita Ghosh et al.   STEM CELLS

Assessment of F/HN-Pseudotyped Lentivirus as a Clinically Relevant Vector for Lung Gene Therapy

(2012) Uta Griesenbach et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Sputum Biomarkers of Inflammation and Lung Function Decline in Children with Cystic Fibrosis

(2012) Scott D. Sagel et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Ivacaftor potentiation of multiple CFTR channels with gating mutations

(2012) Haihui Yu et al.   Journal of Cystic Fibrosis

Microvesicle-associated AAV Vector as a Novel Gene Delivery System

(2012) Casey A Maguire et al.   MOLECULAR THERAPY

Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung

(2012) Alejandro A. Pezzulo et al.   NATURE

Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria

(2012) G. Gasiunas et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity

(2012) M. Jinek et al.   SCIENCE

Isolation and In Vitro Characterization of Basal and Submucosal Gland Duct Stem/Progenitor Cells from Human Proximal Airways

(2012) Ahmed E. Hegab et al.   Stem Cells Translational Medicine

Lentiviral Vector Gene Transfer to Porcine Airways

(2012) Patrick L Sinn et al.   Molecular Therapy-Nucleic Acids

Pre-clinical evaluation of three non-viral gene transfer agents for cystic fibrosis after aerosol delivery to the ovine lung

(2011) G McLachlan et al.   GENE THERAPY

Retinal Degeneration Progression Changes Lentiviral Vector Cell Targeting in the Retina

(2011) Maritza Calame et al.   PLoS One

Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for theF508del-CFTRmutation

(2011) J P Clancy et al.   THORAX

Toward Gene Therapy for Cystic Fibrosis Using a Lentivirus Pseudotyped With Sendai Virus Envelopes

(2010) Katsuyuki Mitomo et al.   MOLECULAR THERAPY

Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition

(2010) Alessandro Luciani et al.   NATURE CELL BIOLOGY

Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-CFTRMutation

(2010) Frank J. Accurso et al.   NEW ENGLAND JOURNAL OF MEDICINE

Cystic Fibrosis Pigs Develop Lung Disease and Exhibit Defective Bacterial Eradication at Birth

(2010) D. A. Stoltz et al.   Science Translational Medicine

Cystic Fibrosis Pulmonary Guidelines

(2009) Patrick A. Flume et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Single-dose lentiviral gene transfer for lifetime airway gene expression

(2009) Alice G. Stocker et al.   JOURNAL OF GENE MEDICINE

CFTR Functions as a Bicarbonate Channel in Pancreatic Duct Cells

(2009) Hiroshi Ishiguro et al.   JOURNAL OF GENERAL PHYSIOLOGY

Directed Evolution of a Novel Adeno-associated Virus (AAV) Vector That Crosses the Seizure-compromised Blood–Brain Barrier (BBB)

(2009) Steven J Gray et al.   MOLECULAR THERAPY

Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770

(2009) F. Van Goor et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients

(2008) Steven J. Howe et al.   JOURNAL OF CLINICAL INVESTIGATION

Frequency and Spectrum of Genomic Integration of Recombinant Adeno-Associated Virus Serotype 8 Vector in Neonatal Mouse Liver

(2008) K. Inagaki et al.   JOURNAL OF VIROLOGY

Lentivirus Vector Can Be Readministered to Nasal Epithelia without Blocking Immune Responses

(2008) P. L. Sinn et al.   JOURNAL OF VIROLOGY

Adeno-Associated Virus Vector Genomes Persist as Episomal Chromatin in Primate Muscle

(2008) M. Penaud-Budloo et al.   JOURNAL OF VIROLOGY

CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression

(2008) Stephen C Hyde et al.   NATURE BIOTECHNOLOGY