ArticleGene therapy2014
shRNA-induced saturation of the microRNA pathway in the rat brain.
Article in Gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
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- How Soon is Soon Enough? Consideration of Timing and Disease Etiology for microRNAs in Epilepsy.Epilepsy currents · 2025Review
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- Pathogen infection alters the gene expression landscape of transposable elements in Drosophila melanogaster.G3 (Bethesda, Md.) · 2024Article
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- miR-AB, a miRNA-based shRNA viral toolkit for multicolor-barcoded multiplex RNAi at a single-cell level.EMBO reports · 2022Article
- RISC-y Business: Limitations of Short Hairpin RNA-Mediated Gene Silencing in the Brain and a Discussion of CRISPR/Cas-Based Alternatives.Frontiers in molecular neuroscience · 2022Review
- Non-coding RNA therapeutics for cardiac regeneration.Cardiovascular research · 2021Review
- MicroRNAs as regulators of brain function and targets for treatment of epilepsy.Nature reviews. Neurology · 2020Review
- A systems approach delivers a functional microRNA catalog and expanded targets for seizure suppression in temporal lobe epilepsy.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Viral infection impacts transposable element transcript amounts inProceedings of the National Academy of Sciences of the United States of America · 2020Article
- CRISPR therapy towards an HIV cure.Briefings in functional genomics · 2020Article
- Cross-species genetic screens to identify kinase targets for APP reduction in Alzheimer's disease.Human molecular genetics · 2019Article
- Enhancement of gene knockdown efficiency by CNNC motifs in the intronic shRNA precursor.Genes & genomics · 2019Article
- A hippocampus to prefrontal cortex neural pathway inhibits food motivation through glucagon-like peptide-1 signaling.Molecular psychiatry · 2018 · on this mapArticle
- Safe and Efficient Silencing with a Pol II, but Not a Pol lII, Promoter Expressing an Artificial miRNA Targeting Human Huntingtin.Molecular therapy. Nucleic acids · 2017Article
- Viral delivery of shRNA to amygdala neurons leads to neurotoxicity and deficits in Pavlovian fear conditioning.Neurobiology of learning and memory · 2015Article
- Reducing Ventral Tegmental Dopamine D2 Receptor Expression Selectively Boosts Incentive Motivation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA interference (RNAi) is a powerful strategy for unraveling gene function and for drug target validation, but exogenous expression of short hairpin RNAs (shRNAs) has been associated with severe side effects. These may be caused by saturation of the microRNA pathway. This study shows degenerative changes in cell morphology and intrusion of blood vessels after transduction of the ventromedial hypothalamus (VMH) of rats with a shRNA expressing adeno-associated viral (AAV) vector. To investigate whether saturation of the microRNA pathway has a role in the observed side effects, expression of neuronal microRNA miR-124 was used as a marker. Neurons transduced with the AAV vector carrying the shRNA displayed a decrease in miR-124 expression. The decreased expression was unrelated to shRNA sequence or target and observed as early as 1 week after injection. In conclusion, this study shows that the tissue response after AAV-directed expression of a shRNA to the VMH is likely to be caused by shRNA-induced saturation of the microRNA pathway. We recommend controlling for miR-124 expression when using RNAi as a tool for studying (loss of) gene function in the brain as phenotypic effects caused by saturation of the RNAi pathway might mask true effects of specific downregulation of the shRNA target.
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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.