Human pre-mRNAs contain on average eight expressed sequences (exons) with an average length of 150 nt and up to 60 intervening sequences (introns) which can vary in length between 35 and 10,000 nt, therefore comprising up to 90 % of each transcriptional unit. In the nucleus, ribonucleoprotein complexes called spliceosomes recognize exon-intron boundaries and catalyze the precise removal of introns and subsequent joining of exons in a process called RNA splicing [105] [106] [107] . Additionally, each primary transcript can yield different mature RNAs through alternative splicing, thereby expanding the information content and versatility of the transcriptome, e.g. through the production of protein isoforms. A recent study of 10,000 human genes revealed, that at least 70 % of all multi-exon genes are alternatively spliced [108] . There are several different types of alternative splicing, amongst others affecting transcription start sites, splice sites, polyadenylation sites or even whole introns and exons. Disruptions of these intricate splicing patterns are tightly coupled with human pathophysiology, either as a determinant or a direct cause of disease or as a modifier of disease susceptibility and severity [109] . Among these diseases are -thalassemia, cystic fibrosis, muscular dystrophies, Frasier syndrome, certain kinds of dementia and cancer. A more de-tailed description of the underlying mechanisms is beyond the focus of this article and can be found in a number of reviews [110] [111] [112] [113] . López-Bigas et al. [114] proposed that 60 % of mutations that cause disease lead to splicing defects rather than changes in the amino acid sequence. Two common forms of mutations are depicted in Fig. (3B) . On the one hand, a mutation in the splice donor can favor recognition of a cryptic splice donor and result in a mutant mRNA containing additional intronic sequences (part I). On the other hand, a mutation in the splice acceptor can lead to skipping of a whole exon and result in a shortened mRNA (part II). Both scenarios have been used in the context of antisense oligonucleotide-mediated approaches targeting alternative splicing. The use of antisense oligonucleotides interacting with mRNA to affect protein production goes back some 20 years [115, 116] . Since then, three principle mechanisms have been exploited for this purpose (for a review see: [117, 118] ): (I) the oligonucleotide/RNA duplex forms a substrate for endogenous RNase H, leading to mRNA cleavage; (II) the oligonucleotide/RNA duplex prevents the productive assembly of the ribosomal complex or arrests a ribosomal complex already engaged in translation, in both cases affecting protein biosynthesis; (III) the oligonucleotide/RNA duplex alters pre-mRNA splicing in the nucleus. The following section will focus on the last approach with the aim to treat splicing disorders and give examples of possible applications for CPPs in this context.