2020年1月28日
Highly efficient gene silencing in mouse brain by overhanging-duplex oligonucleotides via intraventricular route.
FEBS letters
- 巻
- 594
- 号
- 9
- 開始ページ
- 1413
- 終了ページ
- 1423
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1002/1873-3468.13742
Gapmer-type antisense oligonucleotides have not yet been approved for the treatment of central nervous system diseases, whereas steric-blocking-type antisense oligonucleotides have been well-developed for clinical use. We here characterize a new type of double-stranded oligonucleotides, overhanging-duplex oligonucleotides, which are composed of the parent gapmer and its extended complementary RNA. By intracerebroventricular injection, overhanging oligonucleotides show greater silencing potency with more efficient delivery into mouse brains than the parent single-stranded gapmer. Structure-activity relationship analyses reveal that the potency enhancement requires 13-mer or more overhanging oligonucleotides with a phosphorothioate backbone. Overhanging oligonucleotides provide a new platform of therapeutic oligonucleotides for gene modulation in the central nervous system.
- ID情報
-
- DOI : 10.1002/1873-3468.13742
- PubMed ID : 31990989