Emerging Therapeutic Approaches for Cystic Fibrosis. From Gene Editing to Personalized Medicine

PEGylated enhanced cell penetrating peptide nanoparticles for lung gene therapy

(2018) Gizem Osman et al.   JOURNAL OF CONTROLLED RELEASE

Detection of CFTR function and modulation in primary human nasal cell spheroids

(2018) John J. Brewington et al.   Journal of Cystic Fibrosis

Translational research to enable personalized treatment of cystic fibrosis

(2018) Marne C. Hagemeijer et al.   Journal of Cystic Fibrosis

Discovery of 4-[(2R,4R)-4-({[1-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl}amino)-7-(difluoromethoxy)-3,4-dihydro-2H-chromen-2-yl]benzoic Acid (ABBV/GLPG-2222), a Potent Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Corrector for the Treatment of Cystic Fibrosis

(2018) Xueqing Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of N-(3-Carbamoyl-5,5,7,7-tetramethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-2-yl)-lH-pyrazole-5-carboxamide (GLPG1837), a Novel Potentiator Which Can Open Class III Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channels to a High Extent

(2018) Steven E. Van der Plas et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

(2018) Ema Robinson et al.   MOLECULAR THERAPY

Structure-guided combination therapy to potently improve the function of mutant CFTRs

(2018) Guido Veit et al.   NATURE MEDICINE

Induced pluripotent stem cells for treating cystic fibrosis: State of the science

(2018) Bette S. Pollard et al.   PEDIATRIC PULMONOLOGY

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

The long and winding road: stem cells for cystic fibrosis

(2017) Massimo Conese et al.   EXPERT OPINION ON BIOLOGICAL 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

The HDAC inhibitor SAHA does not rescue CFTR membrane expression in Cystic Fibrosis

(2017) Anne Bergougnoux et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

CRISPR Editing Technology in Biological and Biomedical Investigation

(2017) Martyn K. White et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice

(2017) Jeff R. Crosby et al.   Journal of Cystic Fibrosis

Pharmacokinetics and safety of cavosonstat (N91115) in healthy and cystic fibrosis adults homozygous for F 508 DEL - CFTR

(2017) Scott H. Donaldson et al.   Journal of Cystic Fibrosis

Correlation of sweat chloride and percent predicted FEV1 in cystic fibrosis patients treated with ivacaftor

(2017) Meredith C. Fidler et al.   Journal of Cystic Fibrosis

A common mechanism for CFTR potentiators

(2017) Han-I Yeh et al.   JOURNAL OF GENERAL PHYSIOLOGY

Tezacaftor–Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis

(2017) Steven M. Rowe et al.   NEW ENGLAND JOURNAL OF MEDICINE

Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del

(2017) Jennifer L. Taylor-Cousar et al.   NEW ENGLAND JOURNAL OF MEDICINE

Inhaled Drug Therapy 2016: The Year in Review

(2017) Rajiv Dhand   Respiratory Care

Correction of CFTR function in nasal epithelial cells from cystic fibrosis patients predicts improvement of respiratory function by CFTR modulators

(2017) Iwona M. Pranke et al.   Scientific Reports

Efficacy and safety of lumacaftor and ivacaftor in patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTR : a randomised, placebo-controlled phase 3 trial

(2017) Felix Ratjen et al.   Lancet Respiratory Medicine

Assessment of safety and efficacy of long-term treatment with combination lumacaftor and ivacaftor therapy in patients with cystic fibrosis homozygous for the F508del-CFTR mutation (PROGRESS): a phase 3, extension study

(2017) Michael W Konstan et al.   Lancet Respiratory Medicine

Generation of Induced Progenitor-like Cells from Mature Epithelial Cells Using Interrupted Reprogramming

(2017) Li Guo et al.   Stem Cell Reports

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

Augmentation of CFTR maturation by S-nitrosoglutathione reductase

(2016) Khalequz Zaman et al.   AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY

Restoration of R117H CFTR folding and function in human airway cells through combination treatment with VX-809 and VX-770

(2016) Martina Gentzsch et al.   AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY

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

Leveraging Rules of Nonsense-Mediated mRNA Decay for Genome Engineering and Personalized Medicine

(2016) Maximilian W. Popp et al.   CELL

Cystic fibrosis

(2016) Stacey L. Martiniano et al.   CURRENT OPINION IN PEDIATRICS

EPAC1 activation by cAMP stabilizes CFTR at the membrane by promoting its interaction with NHERF1

(2016) Miguel J. Lobo et al.   JOURNAL OF CELL SCIENCE

Non-viral gene therapy: Gains and challenges of non-invasive administration methods

(2016) Marianna Foldvari et al.   JOURNAL OF CONTROLLED RELEASE

32 Properties of a novel F508del-CFTR corrector FDL169

(2016) M. Zawistoski et al.   Journal of Cystic Fibrosis

Rattlesnake Phospholipase A2 Increases CFTR-Chloride Channel Current and Corrects ∆F508CFTR Dysfunction: Impact in Cystic Fibrosis

(2016) Grazyna Faure et al.   JOURNAL OF MOLECULAR BIOLOGY

From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations

(2016) Gudio Veit et al.   MOLECULAR BIOLOGY OF THE CELL

Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

(2016) Johanna F. Dekkers et al.   Science Translational Medicine

Analysis of gene repair tracts from Cas9/gRNA double-stranded breaks in the human CFTR gene

(2016) Jennifer A. Hollywood et al.   Scientific Reports

Modeling Cystic Fibrosis Using Pluripotent Stem Cell-Derived Human Pancreatic Ductal Epithelial Cells

(2016) Senem Simsek et al.   Stem Cells Translational Medicine

Capturing the Direct Binding of CFTR Correctors to CFTR by Using Click Chemistry

(2015) Chandrima Sinha et al.   CHEMBIOCHEM

CFTR Inactivation by Lentiviral Vector-mediated RNA Interference and CRISPR-Cas9 Genome Editing in Human Airway Epithelial Cells

(2015) Jessica Bellec et al.   CURRENT GENE THERAPY

Challenges in CRISPR/CAS9 Delivery: Potential Roles of Nonviral Vectors

(2015) Ling Li et al.   HUMAN GENE THERAPY

Correction of a Cystic Fibrosis Splicing Mutation by Antisense Oligonucleotides

(2015) Susana Igreja et al.   HUMAN MUTATION

Ivacaftor as salvage therapy in a patient with cystic fibrosis genotype F508del/R117H/IVS8-5T

(2015) S. Carter et al.   Journal of Cystic Fibrosis

Origins of Cystic Fibrosis Lung Disease

(2015) David A. Stoltz et al.   NEW ENGLAND JOURNAL OF MEDICINE

Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR

(2015)   NEW ENGLAND JOURNAL OF MEDICINE

Inflammation and its genesis in cystic fibrosis

(2015) David P. Nichols et al.   PEDIATRIC PULMONOLOGY

Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy

(2015) Panagiotis Mastorakos et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

Measurements of Functional Responses in Human Primary Lung Cells as a Basis for Personalized Therapy for Cystic Fibrosis

(2015) Nikhil T. Awatade et al.   EBioMedicine

VX-809 and Related Corrector Compounds Exhibit Secondary Activity Stabilizing Active F508del-CFTR after Its Partial Rescue to the Cell Surface

(2014) Paul D.W. Eckford et al.   CHEMISTRY & BIOLOGY

Biosafety of Recombinant Adeno-associated Virus Vectors

(2014) David Dismuke et al.   CURRENT GENE THERAPY

Biosynthesis of cystic fibrosis transmembrane conductance regulator

(2014) Iwona M. Pranke et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

The relative frequency of CFTR mutation classes in European patients with cystic fibrosis

(2014) K. De Boeck et al.   Journal of Cystic Fibrosis

Some gating potentiators, including VX-770, diminish  F508-CFTR functional expression

(2014) G. Veit et al.   Science Translational Medicine

Potentiator ivacaftor abrogates pharmacological correction of  F508 CFTR in cystic fibrosis

(2014) D. M. Cholon et al.   Science Translational Medicine

Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

(2014) Jessica LaRusch et al.   PLoS Genetics

Ataluren for the treatment of nonsense-mutation cystic fibrosis: a randomised, double-blind, placebo-controlled phase 3 trial

(2014) Eitan Kerem et al.   Lancet Respiratory Medicine

Synthetic Aminoglycosides Efficiently Suppress Cystic Fibrosis Transmembrane Conductance Regulator Nonsense Mutations and Are Enhanced by Ivacaftor

(2013) Xiaojiao Xue et al.   AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

Corrector VX-809 stabilizes the first transmembrane domain of CFTR

(2013) Tip W. Loo et al.   BIOCHEMICAL PHARMACOLOGY

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

(2013) Gerald Schwank et al.   Cell Stem Cell

Revertants, Low Temperature, and Correctors Reveal the Mechanism of F508del-CFTR Rescue by VX-809 and Suggest Multiple Agents for Full Correction

(2013) Carlos M. Farinha et al.   CHEMISTRY & BIOLOGY

Discovery of novel potent ΔF508-CFTR correctors that target the nucleotide binding domain

(2013) Norbert Odolczyk et al.   EMBO Molecular Medicine

CFTR: Effect of ICL2 and ICL4 amino acids in close spatial proximity on the current properties of the channel

(2013) Arnaud Billet et al.   Journal of Cystic Fibrosis

Cystic fibrosis transmembrane conductance regulator-mRNA delivery: a novel alternative for cystic fibrosis gene therapy

(2013) Nadine Bangel-Ruland et al.   JOURNAL OF GENE MEDICINE

VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1

(2013) Hong Yu Ren et al.   MOLECULAR BIOLOGY OF THE CELL

Functional architecture of the CFTR chloride channel

(2013) Paul Linsdell   MOLECULAR MEMBRANE BIOLOGY

Mechanism-based corrector combination restores ΔF508-CFTR folding and function

(2013) Tsukasa Okiyoneda et al.   Nature Chemical Biology

A functional CFTR assay using primary cystic fibrosis intestinal organoids

(2013) Johanna F Dekkers et al.   NATURE MEDICINE

Vx-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle

(2013) Kang-Yang Jih et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

HGF Stimulation of Rac1 Signaling Enhances Pharmacological Correction of the Most Prevalent Cystic Fibrosis Mutant F508del-CFTR

(2012) Sónia Moniz et al.   ACS Chemical Biology

Endogenous Lung Regeneration

(2012) Jason Rock et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Ivacaftor in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation

(2012) Patrick A. Flume et al.   CHEST

mRNA as a Versatile Tool for Exogenous Protein Expression

(2012) Andreas N. Kuhn et al.   CURRENT GENE THERAPY

Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein

(2012) Lihua He et al.   FASEB JOURNAL

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Potentiator VX-770 (Ivacaftor) Opens the Defective Channel Gate of Mutant CFTR in a Phosphorylation-dependent but ATP-independent Manner

(2012) Paul D. W. Eckford et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Ivacaftor potentiation of multiple CFTR channels with gating mutations

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

Increased Selectivity toward Cytoplasmic versus Mitochondrial Ribosome Confers Improved Efficiency of Synthetic Aminoglycosides in Fixing Damaged Genes: A Strategy for Treatment of Genetic Diseases Caused by Nonsense Mutations

(2012) Jeyakumar Kandasamy et al.   JOURNAL OF MEDICINAL CHEMISTRY

Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell

(2012) Shiro Yui et al.   NATURE MEDICINE

Regulatory domain phosphorylation to distinguish the mechanistic basis underlying acute CFTR modulators

(2011) Louise C. Pyle et al.   AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY

Identification of a NBD1-Binding Pharmacological Chaperone that Corrects the Trafficking Defect of F508del-CFTR

(2011) Heidi M. Sampson et al.   CHEMISTRY & BIOLOGY

Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis

(2011) M. Wilschanski et al.   EUROPEAN RESPIRATORY JOURNAL

Supercoiled Minivector DNA resists shear forces associated with gene therapy delivery

(2011) D J Catanese et al.   GENE THERAPY

Disruption of cytokeratin-8 interaction with F508del-CFTR corrects its functional defect

(2011) Julien Colas et al.   HUMAN MOLECULAR GENETICS

Cystic Fibrosis: A New Target for 4-Imidazo[2,1-b]thiazole-1,4-dihydropyridines

(2011) Roberta Budriesi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Suppression of CFTR premature termination codons and rescue of CFTR protein and function by the synthetic aminoglycoside NB54

(2011) Steven M. Rowe et al.   JOURNAL OF MOLECULAR MEDICINE-JMM

A CFTR Potentiator in Patients with Cystic Fibrosis and theG551DMutation

(2011) Bonnie W. Ramsey et al.   NEW ENGLAND JOURNAL OF MEDICINE

Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809

(2011) F. Van Goor et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

CFTR: folding, misfolding and correcting the ΔF508 conformational defect

(2011) Gergely L. Lukacs et al.   TRENDS IN MOLECULAR MEDICINE

Ataluren (PTC124) Induces Cystic Fibrosis Transmembrane Conductance Regulator Protein Expression and Activity in Children with Nonsense Mutation Cystic Fibrosis

(2010) Isabelle Sermet-Gaudelus et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Cystic fibrosis transmembrane conductance regulator protein repair as a therapeutic strategy in cystic fibrosis

(2010) Peter A Sloane et al.   CURRENT OPINION IN PULMONARY MEDICINE

Potentiation of Disease-associated Cystic Fibrosis Transmembrane Conductance Regulator Mutants by Hydrolyzable ATP Analogs

(2010) Haruna Miki et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Cystic Fibrosis-causing Mutation ΔF508 Affects Multiple Steps in Cystic Fibrosis Transmembrane Conductance Regulator Biogenesis

(2010) Patrick H. Thibodeau et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Small molecule correctors of F508del-CFTR discovered by structure-based virtual screening

(2010) Ori Kalid et al.   JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

Rescue of the protein folding defect in cystic fibrosis in vitro by the investigational small molecule, VX-809

(2010) F. Van Goor et al.   Journal of Cystic Fibrosis

Correction of the  Phe508 Cystic Fibrosis Transmembrane Conductance Regulator Trafficking Defect by the Bioavailable Compound Glafenine

(2010) R. Robert et al.   MOLECULAR PHARMACOLOGY

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

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

Hsp 70/Hsp 90 organizing protein as a nitrosylation target in cystic fibrosis therapy

(2010) N. V. Marozkina et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung

(2010) J. L. McQualter et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Cystic Fibrosis Respiratory Epithelial Cell Chronically Treated by Miglustat Acquires a Non–Cystic Fibrosis–Like Phenotype

(2009) Caroline Norez et al.   AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

Correctors Enhance Maturation of ΔF508 CFTR by Promoting Interactions between the Two Halves of the Molecule

(2009) Tip W. Loo et al.   BIOCHEMISTRY

Deletion of CFTR Translation Start Site Reveals Functional Isoforms of the Protein in CF Patients

(2009) Anabela S. Ramalho et al.   CELLULAR PHYSIOLOGY AND BIOCHEMISTRY

Non-viral vectors in cystic fibrosis gene therapy: recent developments and future prospects

(2009) IA Pringle et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Development of Novel Aminoglycoside (NB54) with Reduced Toxicity and Enhanced Suppression of Disease-Causing Premature Stop Mutations

(2009) Igor Nudelman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Rescue of Functional F508del Cystic Fibrosis Transmembrane Conductance Regulator by Vasoactive Intestinal Peptide in the Human Nasal Epithelial Cell Line JME/CF15

(2009) S. Rafferty et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Gating of the CFTR Cl−channel by ATP-driven nucleotide-binding domain dimerisation

(2009) Tzyh-Chang Hwang et al.   JOURNAL OF PHYSIOLOGY-LONDON

Cystic fibrosis

(2009) Brian P O'Sullivan et al.   LANCET

A Small-Molecule Modulator Interacts Directly with  Phe508-CFTR to Modify Its ATPase Activity and Conformational Stability

(2009) L. Wellhauser et al.   MOLECULAR PHARMACOLOGY

Reduced histone deacetylase 7 activity restores function to misfolded CFTR in cystic fibrosis

(2009) Darren M Hutt et al.   Nature Chemical Biology

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

CFTR Function and Prospects for Therapy

(2008) John R. Riordan   Annual Review of Biochemistry

Correctors promote folding of the CFTR in the endoplasmic reticulum

(2008) Tip W. Loo et al.   BIOCHEMICAL JOURNAL

Direct interaction of a small-molecule modulator with G551D-CFTR, a cystic fibrosis-causing mutation associated with severe disease

(2008) Stan Pasyk et al.   BIOCHEMICAL JOURNAL

Potents-cis-Locked Bithiazole Correctors of ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator Cellular Processing for Cystic Fibrosis Therapy⊥

(2008) Gui Jun Yu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Parallel Improvement of Sodium and Chloride Transport Defects by Miglustat (n-Butyldeoxynojyrimicin) in Cystic Fibrosis Epithelial Cells

(2008) S. Noel et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations: a prospective phase II trial

(2008) Eitan Kerem et al.   LANCET

ATP hydrolysis-driven gating in cystic fibrosis transmembrane conductance regulator

(2008) D. Muallem et al.   PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES

Preclinical Evidence that Sildenafil and Vardenafil Activate Chloride Transport in Cystic Fibrosis

(2007) Bob Lubamba et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE