| First Author | Nishina K | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7969 | PubMed ID | 26258894 |
| Mgi Jnum | J:224998 | Mgi Id | MGI:5689950 |
| Doi | 10.1038/ncomms8969 | Citation | Nishina K, et al. (2015) DNA/RNA heteroduplex oligonucleotide for highly efficient gene silencing. Nat Commun 6:7969 |
| abstractText | Antisense oligonucleotides (ASOs) are recognized therapeutic agents for the modulation of specific genes at the post-transcriptional level. Similar to any medical drugs, there are opportunities to improve their efficacy and safety. Here we develop a short DNA/RNA heteroduplex oligonucleotide (HDO) with a structure different from double-stranded RNA used for short interfering RNA and single-stranded DNA used for ASO. A DNA/locked nucleotide acid gapmer duplex with an alpha-tocopherol-conjugated complementary RNA (Toc-HDO) is significantly more potent at reducing the expression of the targeted mRNA in liver compared with the parent single-stranded gapmer ASO. Toc-HDO also improves the phenotype in disease models more effectively. In addition, the high potency of Toc-HDO results in a reduction of liver dysfunction observed in the parent ASO at a similar silencing effect. HDO technology offers a novel concept of therapeutic oligonucleotides, and the development of this molecular design opens a new therapeutic field. |
