There is provided herein, an oligonucleotide directed against a target gene, wherein the oligonucleotide is capable of hybridizing to at least a portion of a nucleic acid sequence encoding the gene under stringent conditions, and wherein, at least one nucleotide of the oligonucleotide is 2-amino-2'- deoxyadenosine (DAP); and the internucleoside linkages of the oligonucleotide comprises at least three alternating segments, each segment consisting of either at least one phosphorothioate or at least one phosphodiester bond.