Open AccessPeptide Dendrimer–Lipid Conjugates as DNA and siRNA Transfection Reagents: Role of Charge Distribution Across Generations
Author(s) -
Marc Heitz,
Albert Kwok,
Gabriela A. Eggimann,
Florian Hollfelder,
Tamis Darbre,
JeanLouis Reymond
Publication year - 2017
Publication title -
chimia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.387
H-Index - 55
eISSN - 2673-2424
pISSN - 0009-4293
DOI - 10.2533/chimia.2017.220
Subject(s) - dendrimer , transfection , nucleic acid , reagent , dna , gene delivery , chemistry , biophysics , combinatorial chemistry , peptide , conjugate , nanotechnology , biochemistry , biology , gene , materials science , organic chemistry , mathematical analysis , mathematics
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.