Elucidation of the uptake of single-stranded oligonucleotides into living cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18853
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: National Center of Neurology and Psychiatry (2016); Hokkaido University (2015)
• Principal Investigator: Takahashi Masayuki 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第四部, 流動研究員 (30743778)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: SIDT2 / Gymnosis / 核酸医薬

Outline of Final Research Achievements

Single-stranded oligonucleotides (ssOligos) are efficiently taken up by living cells without the use of　transfection reagents. This phenomenon called ‘gymnosis’ enables the sequence-specific silencing of target genes in various types of cells. Several antisense ssOligos are used for the treatment of human diseases. However, the molecular mechanism underlying the uptake of naked ssOligos into cells remains to be elucidated. We showed that the uptake of naked ssOligos into cells is significantly downregulated by knockdown of SIDT2. Furthermore, knockdown of SIDT2 inhibited the effect of antisense RNA mediated by gymnosis. Overexpression of SIDT2 enhanced the uptake of naked ssOligos into cells, while a single amino acid mutation in SIDT2 abolished this effect. Our findings highlight the mechanism of extra- and intracellular RNA transport and may contribute to the further development of nucleic acid-based therapies.

Free Research Field

分子生物学