ArticleGene therapy2009
Doxycycline-controlled splicing modulation by regulated antisense U7 snRNA expression cassettes.
Article in Gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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
13 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- RNA-Based Therapeutic Technology.International journal of molecular sciences · 2023Review
- CRISPR-Trap: a clean approach for the generation of gene knockouts and gene replacements in human cells.Molecular biology of the cell · 2018Article
- Overexpression of miR-210 and its significance in ischemic tissue damage.Scientific reports · 2017Article
- Somatic Therapy of a Mouse SMA Model with a U7 snRNA Gene Correcting SMN2 Splicing.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Identification of Interactions in the NMD Complex Using Proximity-Dependent Biotinylation (BioID).PloS one · 2016Article
- A fluorescent approach for identifying P2X1 ligands.Neuropharmacology · 2015Article
- Splicing changes in SMA mouse motoneurons and SMN-depleted neuroblastoma cells: evidence for involvement of splicing regulatory proteins.RNA biology · 2014Article
- Article
- The Krüppel-associated box repressor domain can induce reversible heterochromatization of a mouse locus in vivo.The Journal of biological chemistry · 2012Article
- Therapeutic developments in spinal muscular atrophy.Therapeutic advances in neurological disorders · 2010Article
- Progress in therapeutic antisense applications for neuromuscular disorders.European journal of human genetics : EJHG · 2010Review
- Trans-splicing-mediated improvement in a severe mouse model of spinal muscular atrophy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many diseases affect pre-mRNA splicing, and alternative splicing is a major source of proteome diversity and an important mechanism for modulating gene expression. The ability to regulate a specific splicing event is therefore desirable; for example, to understand splicing-associated pathologies. We have developed methods based on modified U7 snRNAs, which allow us to induce efficient skipping or inclusion of selected exons. Here, we have adapted these U7 tools to a regulatable system that relies on a doxycycline-sensitive version of the Krüppel-associated box (KRAB)/KAP1 transcriptional silencing. Co-transduction of target cells with two lentiviral vectors, one carrying the KRAB protein and the other the regulatable U7 cassette, allows a tight regulation of the modified U7 snRNA. No leakage is observed in the repressed state, whereas full induction can be obtained with doxycycline in ng ml(-1) concentrations. Only a few days are necessary for a full switch, and the induction/repression can be repeated over several cycles without noticeable loss of control. Importantly, the U7 expression correlates with splicing correction, as shown for the skipping of an aberrant beta-globin exon created by a thalassaemic mutation and the promotion of exon 7 inclusion in the human SMN2 gene, an important therapeutic target for spinal muscular atrophy.
Indexed as
Identifiers
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.