title: Efficient Transfection of siRNA by Peptide Dendrimer-Lipid Conjugates.
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.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.
authors.forename: Albert
authors.initials: A
authors.lastname: Kwok
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Eggimann
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Heitz
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Reymond
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.
authors.forename: Florian
authors.identifier: 0000-0002-1367-6312
authors.initials: F
authors.lastname: Hollfelder
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.
authors.forename: Tamis
authors.initials: T
authors.lastname: Darbre
mesh_terms: D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection / Q000379:methods*
chemical_list: D050091:Dendrimers; D008055:Lipids; D010455:Peptides; D034741:RNA, Small Interfering
keywords: RNA interference; gene knockdown; peptide dendrimers; siRNA; transfection