ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Sustained miRNA-mediated knockdown of mutant AAT with simultaneous augmentation of wild-type AAT has minimal effect on global liver miRNA profiles.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers.
What it found
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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.
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Who cites it
64 citing papers in PubMed, 115 citations in OpenAlex.
- Advancing dual gene therapy for SFTPC deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Lung-tropic dual AAV-SP-C and microRNA gene therapy attenuates lung injury in mutant Sftpc mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Development of an AAV-delivered microRNA gene therapy for myotonic dystrophy type 1.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- A compact base editor rescues AATD-associated liver and lung disease in mouse models.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Gene therapy then and now: A look back at changes in the field over the past 25 years.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Gene Therapy for Inherited Liver Disease: To Add or to Edit.International journal of molecular sciences · 2024Review
- Biodistribution and safety of a single rAAV3B-AAT vector for silencing and replacement of alpha-1 antitrypsin inMolecular therapy. Methods & clinical development · 2024Article
- Increased expression or activation of TRPML1 reduces hepatic storage of toxic Z alpha-1 antitrypsin.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- RNAi-mediated rheostat for dynamic control of AAV-delivered transgenes.Nature communications · 2023Article
- Mutation-agnostic RNA interference with engineered replacement rescuesLife science alliance · 2023Article
- Multiplexing AAV Serotype-Specific Neutralizing Antibodies in Preclinical Animal Models and Humans.Biomedicines · 2023Article
- Gene Therapy for Rhodopsin Mutations.Cold Spring Harbor perspectives in medicine · 2022Article
- Approaches to Gene Modulation Therapy for ALS.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Liver-directedMolecular therapy. Methods & clinical development · 2022Article
- Evaluation of cytosine base editing and adenine base editing as a potential treatment for alpha-1 antitrypsin deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Dual-function AAV gene therapy reverses late-stage Canavan disease pathology in mice.Frontiers in molecular neuroscience · 2022Article
- Gene Therapy for Rhodopsin-associated Autosomal Dominant Retinitis Pigmentosa.International ophthalmology clinics · 2021Article
- Up-regulation of miR-34b/c by JNK and FOXO3 protects from liver fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Advances in Alpha-1 Antitrypsin Gene Therapy.American journal of respiratory cell and molecular biology · 2020Review
- CHOP and c-JUN up-regulate the mutant Z αThe Journal of biological chemistry · 2020Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
α-1 antitrypsin (AAT) deficiency can exhibit two pathologic states: a lung disease that is primarily due to the loss of AAT's antiprotease function, and a liver disease resulting from a toxic gain-of-function of the PiZ-AAT (Z-AAT) mutant protein. We have developed several recombinant adeno-associated virus (rAAV) vectors that incorporate microRNA (miRNA) sequences targeting the AAT gene while also driving the expression of miRNA-resistant wild-type AAT-PiM (M-AAT) gene, thus achieving concomitant Z-AAT knockdown in the liver and increased expression of M-AAT. Transgenic mice expressing the human PiZ allele treated with dual-function rAAV9 vectors showed that serum PiZ was stably and persistently reduced by an average of 80%. Treated animals showed knockdown of Z-AAT in liver and serum with concomitant increased serum M-AAT as determined by allele-specific enzyme-linked immunosorbent assays (ELISAs). In addition, decreased globular accumulation of misfolded Z-AAT in hepatocytes and a reduction in inflammatory infiltrates in the liver was observed. Results from microarray studies demonstrate that endogenous miRNAs were minimally affected by this treatment. These data suggests that miRNA mediated knockdown does not saturate the miRNA pathway as has been seen with viral vector expression of short hairpin RNAs (shRNAs). This safe dual-therapy approach can be applied to other disorders such as amyotrophic lateral sclerosis, Huntington disease, cerebral ataxia, and optic atrophies.
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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.