摘要 |
PURPOSE: Novel antisense oligos containing one or more antisense sequence to mRNA region with a less secondary structure are provided to improve their target sequence specificity and stability to nuclease activities. CONSTITUTION: The novel antisense (AS) oligos contains one or more antisense sequence to mRNA region with a less secondary structure. Particularly, they are a covalently-closed multiple antisense (CMAS)-oligo, which is constructed to form a closed type by ligation using complementary primer, and a ribbon-type antisense (RiAS)-oligo, which is composed of two loops containing multiple antisense sequences and a stem connecting the two loops that is constructed to by ligation using complementary sequences at both 5 prime ends. The novel AS-oligos are extremely stable to exonuclease activities and show a significant growth inhibition of tumor cells, and thus pharmaceutical compositions containing the novel types of AS-oligos are effective for the treatment of cancer, immune diseases, infectious diseases, and other human diseases caused by aberrant gene expression.
|