the invention provides a method for generating an oligonucleotide with which an exon may be skipped in a pre - mrna and thus excluded from a produced mrna thereof . further provided are methods for altering the secondary structure of an mrna to interfere with splicing processes and uses of the oligonucleotides and methods in the treatment of disease . further provided are pharmaceutical compositions and methods and means for inducing skipping of several exons in a pre - mrna .