A novel cell-penetrating peptide, M918, for efficient delivery of proteins and peptide nucleic acids.
Cell-penetrating peptides (CPPs) have attracted increasing attention in the past decade as a result of their high potential to convey various, otherwise impermeable, bioactive agents across cellular plasma membranes. Albeit different CPPs have proven potent in delivery of different cargoes, there is generally a correlation between high efficacy and cytotoxicity for these peptides. Hence, it is of great importance to find new, non-toxic CPPs with more widespread delivery properties. We present a novel CPP, M918, that efficiently translocates various cells in a non-toxic fashion. In line with most other CPPs, the peptide is internalized mainly via endocytosis, and in particular macropinocytosis, but independent of glycosaminoglycans on the cell surface. In addition, in a splice correction assay using antisense peptide nucleic acid (PNA) conjugated via a disulphide bridge to M918 (M918-PNA), we observed a dose-dependent increase in correct splicing, exceeding the effect of other CPPs. Our data demonstrate that M918 is a novel CPP that can be used to translocate different cargoes inside various cells efficiently.
El-Andaloussi
Samir
S
Department of Neurochemistry, Stockholm University, Stockholm, Sweden. samir@neurochem.su.se
Johansson
Henrik J
HJ
Holm
Tina
T
Langel
Ulo
U
D000595:Amino Acid Sequence; D004705:Endocytosis; D006025:Glycosaminoglycans / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D020135:Peptide Nucleic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D011506:Proteins / Q000008:administration & dosage*; D012326:RNA Splicing / Q000187:drug effects
D006025:Glycosaminoglycans; D020135:Peptide Nucleic Acids; D011506:Proteins