Part II of Fig. (3B) illustrates a phenomenon that represents a strategy for the treatment of Duchenne muscular dystrophy (DMD). DMD is a severe progressive neuromuscular disorder caused by several different mutations in the dystrophin gene that abolish the production of functional protein [140] . Depending on the location of the mutation, the corresponding exon is skipped by covering the responsible splice sites with steric block oligonucleotides. This allows the transcription of internally deleted, but largely functional, dystro-phin proteins and converts a severe DMD into a milder Becker muscular dystrophy phenotype. A more detailed description of this approach and its application in a number of animal models can be found in several excellent recent reviews [141, 145] . Successful systemic delivery of splice switching oligonucleotides with or without chemical modifications (PMO, LNA, OMe) has been accomplished via injection of naked nucleic acids [146, 147] , with the help of viral vectors [148] , through re-implantation of ex vivo manipulated stem cells [149] or in combination with CPPs [150] [151] [152] [153] [154] . For the latter purpose, several studies were carried out with novel derivatives of arginine-rich peptides containing different numbers of non-amino acids, e.g. aminohexanoic acid and/or -alanine. These CPP-PMO conjugates showed higher serum stability, less endosomal trapping and led to efficient exon skipping in myoblasts and mice at lower dosages than the splice switching PMO alone [152, 153] . Yin et al. [154] used a PNA-modified splice-switching oligonucleotide conjugated to Tat, a muscle specific peptide (MSP) or different functional domains of the adenovirus capsid protein VP1 (AAV6, AAV8) and examined exon skipping efficiency in vitro and in vivo. Surprisingly, both after transfection and intramuscular injection, the activity of these PNA-peptide conjugates was not significantly better than that achieved by naked neutral PNA, presumably due to endosomal trapping.