Efficient Transfection of siRNA by Peptide Dendrimer-Lipid Conjugates
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Kwok, A., Eggimann, G., Heitz, M., Reymond, J., Hollfelder, F., & Darbre, T. (2016). Efficient Transfection of siRNA by Peptide Dendrimer-Lipid Conjugates. ChemBioChem, 17 (23), 2223-2229. https://doi.org/10.1002/cbic.201600485
Efficient delivery of small interfering RNA (siRNA) into cells is the basis of target-gene-specific silencing and, ultimately, gene therapy. However, current transfection reagents are relatively inefficient, and very few studies provide the sort of systematic understanding based on structure-activity relationships that would provide rationales for their improvement. This work established peptide dendrimers (administered with cationic lipids) as siRNA transfection reagents and recorded structure-activity relationships that highlighted the importance of positive charge distribution in the two outer layers and a hydrophobic core as key features for efficient performance. These dendrimer-based transfection reagents work as well as highly optimised commercial reagents, yet show less toxicity and fewer off-target effects. Additionally, the degrees of freedom in the synthetic procedure will allow the placing of decisive recognition features to enhance and fine-tune transfection and cell specificity in the future.
gene knockdown, peptide dendrimers, RNA interference, siRNA, transfection
This work was supported by the University of Bern, the Swiss National Science Foundation, the Biotechnology and Biological Sciences Research Council (BBSRC), the Newton Trust, the European Research Council (ERC) and the EU Marie Curie ITN MMBio.
External DOI: https://doi.org/10.1002/cbic.201600485
This record's URL: https://www.repository.cam.ac.uk/handle/1810/261443