The present invention relates to a method of modulating splice site
selection, splicing and alternative, the method comprising the step of
hybridizing an oligonucleotide-protein conjugate to a target pre-mRNA
molecule in a cell or cell extract, wherein the oligonucleotide-protein
conjugate comprises an oligonucleotide moiety which comprises at least
two distinct sequence elements: (i) a nucleic acid sequence that is
complementary to a specific region upstream of the splice site in the
target pre-mRNA molecule; and (ii) an extension containing a protein
binding site sequence element for covalently binding a protein; wherein
the protein moiety comprises a protein capable of modulating splicing of
the splice site upon binding with the protein binding site.