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Efficient Transfection of siRNA by Peptide Dendrimer–Lipid Conjugates
Type of publication
Peer-reviewed
Publikationsform
Original article (peer-reviewed)
Author
Kwok A., Eggimann G. A., Heitz M., Reymond Jean-Louis, Hollfelder F., Darbre T.,
Project
A Chemical Space Approach to Bioactive Peptides
Show all
Original article (peer-reviewed)
Journal
ChemBioChem Communications
Volume (Issue)
17
Page(s)
2223 - 2229
Title of proceedings
ChemBioChem Communications
DOI
10.1002/cbic.201600485
Open Access
URL
https://onlinelibrary.wiley.com/doi/full/10.1002/cbic.201600485
Type of Open Access
Website
Abstract
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.
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