DNA/RNA heteroduplex oligonucleotide for highly efficient gene silencing

Kazutaka Nishina, Wenying Piao, Kie Yoshida-Tanaka, Yumiko Sujino, Tomoko Nishina, Tsuyoshi Yamamoto, Keiko Nitta, Kotaro Yoshioka, Hiroya Kuwahara, Hidenori Yasuhara, Takeshi Baba, Fumiko Ono, Kanjiro Miyata, Koichi Miyake, Punit P. Seth, Audrey Low, Masayuki Yoshida, C. Frank Bennett, Kazunori Kataoka, Hidehiro Mizusawa, Satoshi Obika and Takanori Yokota ()
Additional contact information
Kazutaka Nishina: Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
Wenying Piao: Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
Kie Yoshida-Tanaka: Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
Yumiko Sujino: Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
Tomoko Nishina: Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
Tsuyoshi Yamamoto: Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University
Keiko Nitta: Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
Kotaro Yoshioka: Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
Hiroya Kuwahara: Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
Hidenori Yasuhara: Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University
Takeshi Baba: Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University
Fumiko Ono: The Corporation for Production and Research of Laboratory Primates, 1-16-2 Sakura, Tsukuba-shi, Ibaraki 305-0003, Japan
Kanjiro Miyata: Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Koichi Miyake: Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
Punit P. Seth: Isis Pharmaceuticals
Audrey Low: Isis Pharmaceuticals
Masayuki Yoshida: Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
C. Frank Bennett: Isis Pharmaceuticals
Kazunori Kataoka: Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Hidehiro Mizusawa: Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
Satoshi Obika: Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST)
Takanori Yokota: Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract 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 α-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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms8969 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8969

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms8969

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().