Trial reportThe Journal of clinical investigation1999
Airway epithelial CFTR mRNA expression in cystic fibrosis patients after repetitive administration of a recombinant adenovirus.
Trial report in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.The Cochrane database of systematic reviews · 2016Pooled it
- Development of CpG-Depleted CFTR Plasmid-Based Nanoparticles for Nonviral Gene Therapy in Lung Cystic Fibrosis Disease.The journal of gene medicine · 2026Article
- Four decades of adenovirus gene transfer vectors: History and current use.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Pharmacological and pre-clinical safety profile of rSIV.F/HN, a hybrid lentiviral vector for cystic fibrosis gene therapy.The European respiratory journal · 2025Article
- Review
- Review
- The arc of discovery, from the description of cystic fibrosis to effective treatments.The Journal of clinical investigation · 2024Article
- Current landscape of cystic fibrosis gene therapy.Frontiers in pharmacology · 2024Review
- Endobronchial Aerosolized AAV1.SERCA2a Gene Therapy in a Pulmonary Hypertension Pig Model: Addressing the Lung Delivery Bottleneck.Human gene therapy · 2022Article
- Gene therapy for cystic fibrosis: Challenges and prospects.Frontiers in pharmacology · 2022Review
- Beyond cystic fibrosis transmembrane conductance regulator therapy: a perspective on gene therapy and small molecule treatment for cystic fibrosis.Gene therapy · 2019Review
- Targeted Gene Delivery through the Respiratory System: Rationale for Intratracheal Gene Transfer.Journal of cardiovascular development and disease · 2019Review
- Review
- Lessons learned from lung and liver in-vivo gene therapy: implications for the future.Expert opinion on biological therapy · 2018Review
- Lipid Nanoparticle-Delivered Chemically Modified mRNA Restores Chloride Secretion in Cystic Fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Academic, Foundation, and Industry Collaboration in Finding New Therapies.The New England journal of medicine · 2017Review
- AJRCCM: 100-Year Anniversary. Progress along the Pathway of Discovery Leading to Treatment and Cure of Cystic Fibrosis.American journal of respiratory and critical care medicine · 2017Article
- Barriers to inhaled gene therapy of obstructive lung diseases: A review.Journal of controlled release : official journal of the Controlled Release Society · 2016Review
- The transgenic animal platform for biopharmaceutical production.Transgenic research · 2016Review
- New and emerging targeted therapies for cystic fibrosis.BMJ (Clinical research ed.) · 2016Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
14 authors.
Funding
Abstract
We sought to evaluate the ability of an E1(-), E3(-) adenovirus (Ad) vector (Ad(GV)CFTR.10) to transfer the normal human cystic fibrosis transmembrane conductance regulator (CFTR) cDNA to the airway epithelium of individuals with cystic fibrosis (CF). We administered Ad(GV)CFTR.10 at doses of 3 x 10(6) to 2 x 10(9) plaque-forming units over 9 months by endobronchial spray to 7 pairs of individuals with CF. Each 3-month cycle, we measured vector-derived versus endogenous CFTR mRNA in airway epithelial cells prior to therapy, as well as 3 and 30 days after therapy. The data demonstrate that (a) this strategy appears to be safe; (b) after the first administration, vector-derived CFTR cDNA expression in the CF airway epithelium is dose-dependent, with greater than 5% endogenous CFTR mRNA levels at the higher vector doses; (c) expression is transient, lasting less than 30 days; (d) expression can be achieved with a second administration, but only at intermediate doses, and no expression is observed with the third administration; and (e) the progressive lack of expression with repetitive administration does not closely correlate with induction of systemic anti-Ad neutralizing antibodies. The major advantage of an Ad vector is that it can deliver sufficient levels of CFTR cDNA to the airway epithelium so that CFTR expression protects the lungs from the respiratory manifestations of CF. However, this impressive level of expression is linked to the challenging fact that expression is limited in time. Although this can be initially overcome by repetitive administration, unknown mechanisms eventually limit this strategy, and further repetitive administration does not lead to repetitive expression.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.