ArticlePloS one2012
Cellular cytoskeleton dynamics modulates non-viral gene delivery through RhoGTPases.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Gene Delivery From Granular Scaffolds for Tunable Biologics Manufacturing.Small (Weinheim an der Bergstrasse, Germany) · 2024Article
- Vibropolyfection: coupling polymer-mediated gene delivery to mechanical stimulation to enhance transfection of adherent cells.Journal of nanobiotechnology · 2022Article
- Physical and mechanical cues affecting biomaterial-mediated plasmid DNA delivery: insights into non-viral delivery systems.Journal, genetic engineering & biotechnology · 2021Review
- Article
- Screening a chemically defined extracellular matrix mimetic substrate library to identify substrates that enhance substrate-mediated transfection.Experimental biology and medicine (Maywood, N.J.) · 2020Article
- Pathways Governing Polyethylenimine Polyplex Transfection in Microporous Annealed Particle Scaffolds.Bioconjugate chemistry · 2019Article
- Biomaterial substrate modifications that influence cell-material interactions to prime cellular responses to nonviral gene delivery.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Nucleic acid delivery to mesenchymal stem cells: a review of nonviral methods and applications.Journal of biological engineering · 2019Review
- Free Polyethylenimine Enhances Substrate-Mediated Gene Delivery on Titanium Substrates Modified With RGD-Functionalized Poly(acrylic acid) Brushes.Frontiers in chemistry · 2019Article
- An inhibitor screen identifies histone-modifying enzymes as mediators of polymer-mediated transgene expression from plasmid DNA.Journal of controlled release : official journal of the Controlled Release Society · 2018Article
- It's All in the Delivery: Designing Hydrogels for Cell and Non-viral Gene Therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Review
- Cyclic strain-induced cytoskeletal rearrangement of human periodontal ligament cells via the Rho signaling pathway.PloS one · 2014Article
- The effect of substrate elasticity and actomyosin contractility on different forms of endocytosis.PloS one · 2014Article
- Transfection in the third dimension.Integrative biology : quantitative biosciences from nano to macro · 2013Article
- Matrix-based gene delivery for tissue repair.Current opinion in biotechnology · 2013Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Although it is well accepted that the constituents of the cellular microenvironment modulate a myriad of cellular processes, including cell morphology, cytoskeletal dynamics and uptake pathways, the underlying mechanism of how these pathways influence non-viral gene transfer have not been studied. Transgene expression is increased on fibronectin (Fn) coated surfaces as a consequence of increased proliferation, cell spreading and active engagement of clathrin endocytosis pathway. RhoGTPases mediate the crosstalk between the cell and Fn, and regulate cellular processes involving filamentous actin, in-response to cellular interaction with Fn. Here the role of RhoGTPases specifically Rho, Rac and Cdc42 in modulation of non-viral gene transfer in mouse mesenchymal stem (mMSCs) plated in a fibronectin microenvironment was studied. More than 90% decrease in transgene expression was observed after inactivation of RhoGTPases using difficile toxin B (TcdB) and C3 transferase. Expression of dominant negative RhoA (RhoAT19N), Rac1(Rac1T17N) and Cdc42 (Cdc42T17N) also significantly reduced polyplex uptake and transgene expression. Interactions of cells with Fn lead to activation of RhoGTPases. However, further activation of RhoA, Rac1 and Cdc42 by expression of constitutively active genes (RhoAQ63L, Rac1Q61L and Cdc42Q61L) did not further enhance transgene expression in mMSCs, when plated on Fn. In contrast, activation of RhoA, Rac1 and Cdc42 by expression of constitutively active genes for cells plated on collagen I, which by itself did not increase RhoGTPase activation, resulted in enhanced transgene expression. Our study shows that RhoGTPases regulate internalization and effective intracellular processing of polyplexes that results in efficient gene transfer.
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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.