Photocaged Small Interfering RNA

E. A. Akhmetova; D. V. Kim; A. S. Dome; M. I. Meschaninova; D. S. Novopashina

doi:10.1134/S106816202205003X

Photocaged Small Interfering RNA

Переведенное название: Новый подход к синтезу фотоблокированных малых интерферирующих РНК для активируемой светом РНК-интерференции

E. A. Akhmetova, D. V. Kim, A. S. Dome, M. I. Meschaninova, D. S. Novopashina

Кафедра молекулярной биологии и биотехнологии

Результат исследования: Научные публикации в периодических изданиях › статья › рецензирование

Аннотация

Фоторегулируемые системы – интересный и перспективный инструмент воздействия на экспрессию генов. В данной работе предложен подход к синтезу фоторегулируемых малых интерферирующих РНК (siРНК) для активируемой светом РНК-интерференции. siРНК временно блокируют путем введения на 5'-концы цепей siРНК объемных лигандов через фоторасщепляемый линкер. Введение осуществляют путем активации концевой гидроксильной группы дисукцинимидилкарбонатом с последующим взаимодействием с аминосодержащим лигандом. В качестве функциональных лигандов использованы аминопроизводное холестерина и трилейцин. Продемонстрировано эффективное отщепление группировки, введенной через фоторащепляемый линкер, путем облучения УФ-светом. С использованием предложенного подхода получены siРНК, содержащие остатки холестерина на 5'-конце антисенс- и/или сенс-цепи и направленные на мРНК EGFP (усиленного зеленого флуоресцентного белка). Продемонстрирована возможность фотоактивируемого ингибирования экспрессии гена EGFP в клетках HEK293FT, стабильно экспрессирующих этот белок.

Переведенное название	Новый подход к синтезу фотоблокированных малых интерферирующих РНК для активируемой светом РНК-интерференции
Язык оригинала	английский
Страницы (с-по)	1036-1042
Число страниц	7
Журнал	Russian Journal of Bioorganic Chemistry
Том	48
Номер выпуска	5
DOI	https://doi.org/10.1134/S106816202205003X
Состояние	Опубликовано - окт. 2022

Предметные области OECD FOS+WOS

1.06 БИОЛОГИЧЕСКИЕ НАУКИ
1.04 ХИМИЧЕСКИЕ НАУКИ

Доступ к документу

10.1134/S106816202205003X

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Ссылка на публикацию в Scopus

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title = "Photocaged Small Interfering RNA",

abstract = "Photoregulated systems are interesting and prospective instruments to affect gene expression. An approach to the synthesis of photoregulated siRNA has been proposed for RNA interference activated by light irradiation. For temporary protection, a bulky group has been introduced in siRNA through the photocleavable linker. We have used amino-modified cholesterol and trileucine as bulky ligands, which have been attached to siRNA by the interaction with the hydroxyl group activated with disuccinimidyl carbonate. The efficient UV-induced removal of the ligands introduced through the photocleavable linker has been demonstrated. Using the proposed approach, siRNA molecules bearing cholesterol residues at the 5'-terminus of sense- and/or antisense strands have been synthesized. They were targeted to mRNA of EGFP (enhanced green fluorescent protein). The photoinduced inhibition of the EGFP gene expression in the EGFP-expressing HEK293FT cells has been shown to be possible.",

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author = "Akhmetova, {E. A.} and Kim, {D. V.} and Dome, {A. S.} and Meschaninova, {M. I.} and Novopashina, {D. S.}",

note = "Funding Information: The work was supported by the Russian Foundation of Basic Research (grant no. 19-04-00838) and the State Programs of Fundamental Scientific Research (2021–2023) (121031300042-1). Publisher Copyright: {\textcopyright} 2022, Pleiades Publishing, Ltd.",

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AU - Akhmetova, E. A.

AU - Kim, D. V.

AU - Dome, A. S.

AU - Meschaninova, M. I.

AU - Novopashina, D. S.

N1 - Funding Information: The work was supported by the Russian Foundation of Basic Research (grant no. 19-04-00838) and the State Programs of Fundamental Scientific Research (2021–2023) (121031300042-1). Publisher Copyright: © 2022, Pleiades Publishing, Ltd.

PY - 2022/10

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N2 - Photoregulated systems are interesting and prospective instruments to affect gene expression. An approach to the synthesis of photoregulated siRNA has been proposed for RNA interference activated by light irradiation. For temporary protection, a bulky group has been introduced in siRNA through the photocleavable linker. We have used amino-modified cholesterol and trileucine as bulky ligands, which have been attached to siRNA by the interaction with the hydroxyl group activated with disuccinimidyl carbonate. The efficient UV-induced removal of the ligands introduced through the photocleavable linker has been demonstrated. Using the proposed approach, siRNA molecules bearing cholesterol residues at the 5'-terminus of sense- and/or antisense strands have been synthesized. They were targeted to mRNA of EGFP (enhanced green fluorescent protein). The photoinduced inhibition of the EGFP gene expression in the EGFP-expressing HEK293FT cells has been shown to be possible.

AB - Photoregulated systems are interesting and prospective instruments to affect gene expression. An approach to the synthesis of photoregulated siRNA has been proposed for RNA interference activated by light irradiation. For temporary protection, a bulky group has been introduced in siRNA through the photocleavable linker. We have used amino-modified cholesterol and trileucine as bulky ligands, which have been attached to siRNA by the interaction with the hydroxyl group activated with disuccinimidyl carbonate. The efficient UV-induced removal of the ligands introduced through the photocleavable linker has been demonstrated. Using the proposed approach, siRNA molecules bearing cholesterol residues at the 5'-terminus of sense- and/or antisense strands have been synthesized. They were targeted to mRNA of EGFP (enhanced green fluorescent protein). The photoinduced inhibition of the EGFP gene expression in the EGFP-expressing HEK293FT cells has been shown to be possible.

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