ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Enhancers of adeno-associated virus AAV2 transduction via high throughput siRNA screening.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 23 citations in OpenAlex.
- Enhanced conversion of T cells into CAR T cells by modulation of the MAPK/ERK pathway.Cell reports. Medicine · 2025Article
- Temporal insights into molecular and cellular responses during rAAV production in HEK293T cells.Molecular therapy. Methods & clinical development · 2024Article
- Review
- Casein kinase 2 activity is a host restriction factor for AAV transduction.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- UnravelingFrontiers in oncology · 2024Review
- Predicted deleterious variants in the human genome relevant to gene therapy with adeno-associated virus vectors.Molecular therapy. Methods & clinical development · 2023Article
- Adeno-associated virus (AAV) cell entry: structural insights.Trends in microbiology · 2022Review
- Intracellular trafficking of adeno-associated virus (AAV) vectors: challenges and future directions.Gene therapy · 2021Review
- Review
- Host determinants of adeno-associated viral vector entry.Current opinion in virology · 2017Review
- The SUMOylation Pathway Restricts Gene Transduction by Adeno-Associated Viruses.PLoS pathogens · 2015Article
- Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Intracellular transport of recombinant adeno-associated virus vectors.Gene therapy · 2012Review
- Adeno-associated virus 2 infection requires endocytosis through the CLIC/GEEC pathway.Cell host & microbe · 2011Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Intracellular barriers to adeno-associated virus (AAV) transduction may limit gene delivery. We screened a short interfering RNA (siRNA) library targeting 5,520 genes to help identify pathways that modulate AAV transduction of human endothelium. In replicate screening, 50 pools (three siRNAs per gene) resulted in greater than eightfold reporter gene expression enhancement. Single siRNA confirmation tests demonstrated that at least one siRNA from each of the top 10 pools provided greater than twofold enhancement. Several siRNAs when used together resulted in additive effects and two of the most potent siRNA sequences were enhancers in cultured airway epithelium. However, enhanced transduction was not correlated with mRNA knockdown by quantitative real time PCR, indicating an off-target mechanism. In fact, four of the five most potent siRNAs contained a consensus hexamer region 5'-UGUUUC-3' at positions 2-7 of the antisense strand. The point mutation U4A within this region (but not mutations at positions 1 or 14) disrupted transduction enhancement, indicating a microRNA (miRNA)-like mechanism. Transcription profiling indicated that the hexamer also resulted in perturbation of the interferon pathway via reduced interferon-induced protein 44-like (IFI44L), interferon-inducible myxovirus resistance 1 (MX1), and interferon-induced protein with tetratricopeptide repeats (IFIT5) mRNAs. Direct interferon (α, β, and ω) receptor 2 (IFNAR2) knockdown resulted in greater than twofold transduction enhancement. In addition to providing insight into AAV biology and enhanced transduction, the results demonstrate certain beneficial siRNA off-target effects.
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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.