Modified antisense nucleotides complementary to a section of the human Ha-ras gene

摘要

The invention relates to a specific modified oligonucleotide complementary to a section of the human Hs-ras gene and mRNA, and its use to specifically regulate, modulate, or inhibit expression of the Ha-ras gene, and its use as a pharmaceutical for the treatment of conditions arising from the abnormal expression of the Ha-ras gene, in particular in combination with chemotherapy and radiotherapy. The modified oligodeoxynucleotide according to the invention has the sequence: 5'-TxAxTxTxCxCxGxTxCxAxTx-3'-O-PO2-O-R, wherein x is o or s, with the proviso that x is at least 4 times s and at maximum 9 times s and o means a phosphodiester internucleoside linkage, s means a phosphorothioate internucleoside linkage, R means a C8-C21 alkyl group, -(CH2-CH2O)n-(CH2)m-CH3 or -CH2-CH(OH)CH2O-(CH2)q-CH3 wherein n is an integer from 1 to 6, m is an integer from 0 to 20 and q is an integer from 7 to 20 and A is 2'-deoxyadenosine, G is 2'-deoxyguanosine, C is 2'-deoxycytidine and T is thymadine.