The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
The Internalization Route Resulting in Successful Gene Expression Depends on both Cell Line and Polyethylenimine Polyplex Type
Open accessAbstract
Understanding cellular uptake and intracellular processing of nonviral gene delivery systems is a key aspect in developing more efficient vectors. In this study, the impact of clathrin- and caveolae/lipid-raft-dependent endocytosis on cell entry and overall transfection efficiency of polyethylenimine (PEI) polyplexes was evaluated. Most remarkably, the internalization pathway mediating successful transfection depended on both cell type and polyplex type applied. Colocalization studies with transferrin and cholera toxin B revealed that at least two specific endocytosis pathways--the clathrin-dependent and the lipid-raft-dependent--mediated cellular uptake of PEI polyplexes. With the help of specific uptake inhibitors (chlorpromazine and filipin III), cell-line-dependent variations regarding the route of successful transfection were observed (HUH-7, COS-7, HeLa). In COS-7 cells, the clathrin-dependent pathway was the main contributor to the transfection process. In HUH-7 cells, gene transfer by linear PEI polyplexes succeeded mainly via the clathrin-dependent route, whereas transfection by branched PEI polyplexes was mediated by both pathways. In HeLa cells, both pathways were able to mediate successful gene delivery. However, the lipid-raft-dependent pathway was more relevant. The study also revealed that the concentration window between specific inhibitory function and nonspecific toxicity of the uptake inhibitors was very narrow.
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Self-citationThe great escape: how cationic polyplexes overcome the endosomal barrier
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Polymeric Delivery of Therapeutic Nucleic Acids
Kumar, R., Santa Chalarca, C. F., Bockman, M. R., Bruggen, C. V., Grimme, C. J., Dalal, R. J., Hanson, M. G., Hexum, J. K., & Reineke, T. M. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00997 · Cited by 365
Metadata
- Authors
- von Gersdorff, K., Sanders, N. N., Vandenbroucke, R., De Smedt, S. C., Wagner, E., & Ogris, M.
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 14
- Issue
- 5
- Pages
- 745-753
- ISSN
- 1525-0016 (ISSN-L)
- OpenAlex
- W2016568056
- Cited by
- 314
- References
- 33
- FWCI
- 6.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- von Gersdorff, K., Sanders, N. N., Vandenbroucke, R., De Smedt, S. C., Wagner, E., & Ogris, M. (2006). The Internalization Route Resulting in Successful Gene Expression Depends on both Cell Line and Polyethylenimine Polyplex Type. Molecular Therapy. https://doi.org/10.1016/j.ymthe.2006.07.006
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