A novel cell-penetrating peptide, M918, for efficient delivery of proteins and peptide nucleic acids

Mol Ther. 2007 Oct;15(10):1820-6. doi: 10.1038/sj.mt.6300255. Epub 2007 Jul 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Endocytosis
  • Glycosaminoglycans / metabolism
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Peptide Nucleic Acids / administration & dosage*
  • Peptide Nucleic Acids / pharmacology
  • Proteins / administration & dosage*
  • RNA Splicing / drug effects


  • Glycosaminoglycans
  • Peptide Nucleic Acids
  • Proteins