Improved serum stability and biophysical properties of siRNAs following chemical modifications

Ik Sang Cho; Jung Kim; Do Hwan Lim; Hee Chul Ahn; Hyunggee Kim; Kang Bong Lee; Young Sik Lee

doi:10.1007/s10529-008-9776-4

Improved serum stability and biophysical properties of siRNAs following chemical modifications

Ik Sang Cho, Jung Kim, Do Hwan Lim, Hee Chul Ahn, Hyunggee Kim, Kang Bong Lee, Young Sik Lee

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Small interfering RNAs (siRNAs) which mediate sequence-specific gene silencing through RNA interference have been harnessed for therapeutic applications. Here, we found combinations of modest 2′-ribose siRNA modifications that permit effective gene silencing and improve siRNA stability in human serum. Introduction of as few as two different or identical 2′-ribose modifications at a specific position of either strand, which has been previously suggested to suppress unintended off-target effects, enhances the thermal and thermodynamic stability of siRNA duplexes, and does not alter the overall A-form helical geometry that is required for silencing activity. Our results provide a useful template for the design for therapeutic siRNAs.

Original language	English
Pages (from-to)	1901-1908
Number of pages	8
Journal	Biotechnology letters
Volume	30
Issue number	11
DOIs	https://doi.org/10.1007/s10529-008-9776-4
Publication status	Published - 2008 Nov

Bibliographical note

Funding Information:
Acknowledgements We are grateful to Prof. S. S. Park for critical reading of this manuscript. This research was supported by a grant (07132KFDA689) from the Korea Food and Drug Administration, in 2007.

Keywords

2′-Ribose modification
A-form helix
Melting temperature
RNA interference
Stability
siRNA

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology

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10.1007/s10529-008-9776-4

Cite this

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title = "Improved serum stability and biophysical properties of siRNAs following chemical modifications",

abstract = "Small interfering RNAs (siRNAs) which mediate sequence-specific gene silencing through RNA interference have been harnessed for therapeutic applications. Here, we found combinations of modest 2′-ribose siRNA modifications that permit effective gene silencing and improve siRNA stability in human serum. Introduction of as few as two different or identical 2′-ribose modifications at a specific position of either strand, which has been previously suggested to suppress unintended off-target effects, enhances the thermal and thermodynamic stability of siRNA duplexes, and does not alter the overall A-form helical geometry that is required for silencing activity. Our results provide a useful template for the design for therapeutic siRNAs.",

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note = "Funding Information: Acknowledgements We are grateful to Prof. S. S. Park for critical reading of this manuscript. This research was supported by a grant (07132KFDA689) from the Korea Food and Drug Administration, in 2007.",

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AU - Cho, Ik Sang

AU - Kim, Jung

AU - Lim, Do Hwan

AU - Ahn, Hee Chul

AU - Kim, Hyunggee

AU - Lee, Kang Bong

AU - Lee, Young Sik

N1 - Funding Information: Acknowledgements We are grateful to Prof. S. S. Park for critical reading of this manuscript. This research was supported by a grant (07132KFDA689) from the Korea Food and Drug Administration, in 2007.

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N2 - Small interfering RNAs (siRNAs) which mediate sequence-specific gene silencing through RNA interference have been harnessed for therapeutic applications. Here, we found combinations of modest 2′-ribose siRNA modifications that permit effective gene silencing and improve siRNA stability in human serum. Introduction of as few as two different or identical 2′-ribose modifications at a specific position of either strand, which has been previously suggested to suppress unintended off-target effects, enhances the thermal and thermodynamic stability of siRNA duplexes, and does not alter the overall A-form helical geometry that is required for silencing activity. Our results provide a useful template for the design for therapeutic siRNAs.

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KW - Stability

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Improved serum stability and biophysical properties of siRNAs following chemical modifications

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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