King's College London

Research portal

Histidine-rich designer peptides of the LAH4 family promote cell delivery of a multitude of cargo

Research output: Contribution to journalArticle

Gilles Moulay, Christian Leborgne, A. James Mason, Christopher Aisenbrey, Antoine Kichler, Burkhard Bechinger

Original languageEnglish
Early online date9 Jan 2017
Publication statusPublished - Apr 2017


King's Authors


The histidine-rich designer peptides of the LAH4 family exhibit potent antimicrobial, transfection, transduction and cell penetrating properties. They form non-covalent complexes with their cargo, which often carry a negative overall charge at pH 7.4 and include a large range of molecules and structures such as oligonucleotides, including siRNA and DNA, peptides, proteins, nanodots and adeno-associated viruses. These complexes are thought to enter the cells through an endosomal pathway where the acidification of the organelle is essential for efficient endosomal escape. Biophysical measurements indicate that, upon acidification, almost half the peptides are released from DNA cargo, leading to the suggestion of a self-promoted uptake mechanism where the liberated peptides lyse the endosomal membranes. LAH4 derivatives also help in cellular transduction using lentiviruses. Here we compare the DNA transfection activities of LAH4 derivatives, which vary in overall charge and/or the composition in the hydrophobic core region. In addition, LAH4 is shown to mediate the transport of functional β-galactosidase, a large tetrameric protein of about 0.5 MDa, into the cell interior. Interestingly, the LAH1 peptide efficiently imports this protein while it is inefficient during DNA transfection assays.

Download statistics

No data available

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454