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.
