Histidine-rich cationic amphipathic peptides for plasmid DNA and siRNA delivery.
Amphipathic, pH-responsive, membrane-active peptides such as LAH4 and derivatives thereof have the ability to effectively deliver genes and small interfering RNA (siRNA) into mammalian cells. Their ability to bind and protect nucleic acids and then disrupt membranes when activated at low pH enables them to harness the endocytic machinery to deliver cargo efficiently and with low associated toxicity. This chapter describes protocols for the chemical synthesis of transfection peptides of the LAH4 family, complex formation with nucleic acids, and their use for the in vitro delivery of either plasmid DNA or siRNA into mammalian cell lines.
Laboratoire de Pharmacologie Chimique et Génétique et d'Imagerie, U1022 INSERM, Paris, France. antoine.kichler@parisdescartes.fr
Antoine
A
Kichler
A James
AJ
Mason
Arnaud
A
Marquette
Burkhard
B
Bechinger
D000595:Amino Acid Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D006639:Histidine; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D008156:Luciferases / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D010957:Plasmids / Q000235:genetics*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012542:Scattering, Radiation; D014162:Transfection
D004337:Drug Carriers; D010455:Peptides; D034741:RNA, Small Interfering; D006639:Histidine; D004247:DNA; D008156:Luciferases