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Peptide Dendrimer–Lipid Conjugates as DNA and siRNA Transfection Reagents: Role of Charge Distribution Across Generations

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Transfection reagents are used to deliver DNA and siRNA into cells to achieve genetic manipulations, and may ultimately enable nonviral gene therapy. Progress in transfection reagents is limited by the fact that such reagents cannot be easily optimized due to their polymeric nature and/or difficult synthesis. We have developed a new class of well-defined and easily modifiable transfection reagents in the form of peptide dendrimers. These dendrimers self-assemble with DNA or siRNA and lipofectin to form nanoparticles which efficiently enter mammalian cells and liberate their nucleic acid cargo. By systematically modifying the amino acid sequence of our dendrimers we have found that their transfection efficiency depends on the distribution of positive charges and hydrophobic residues across the dendrimer branches. Positive charges present in all three generations lead to efficient DNA delivery, whereas siRNA delivery requires charges in the outer two generations combined with a hydrophobic dendrimer core.
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Keywords: DENDRIMER; DNA; PEPTIDE; SIRNA; TRANSFECTION

Document Type: Research Article

Affiliations: 1: Department of Chemistry and Biochemistry University of Bern Freiestrasse 3, CH-3012 Bern;, Email: [email protected] 2: Department of Chemistry and Biochemistry University of Bern Freiestrasse 3, CH-3012 Bern 3: Department of Chemistry and Biochemistry University of Bern Freiestrasse 3, CH-3012 Bern;, Email: [email protected]

Publication date: 2017-04-01

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  • International Journal for Chemistry and Official Membership Journal of the Swiss Chemical Society (SCS) and its Divisions

    CHIMIA, a scientific journal for chemistry in the broadest sense, is published 10 times a year and covers the interests of a wide and diverse readership. Contributions from all fields of chemistry and related areas are considered for publication in the form of Review Articles and Notes. A characteristic feature of CHIMIA are the thematic issues, each devoted to an area of great current significance.

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