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

20 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

Access to Document

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.",

keywords = "2′-Ribose modification, A-form helix, Melting temperature, RNA interference, Stability, siRNA",

author = "Cho, \{Ik Sang\} and Jung Kim and Lim, \{Do Hwan\} and Ahn, \{Hee Chul\} and Hyunggee Kim and Lee, \{Kang Bong\} and Lee, \{Young Sik\}",

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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doi = "10.1007/s10529-008-9776-4",

language = "English",

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T1 - Improved serum stability and biophysical properties of siRNAs following chemical modifications

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.

PY - 2008/11

Y1 - 2008/11

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.

AB - 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.

KW - 2′-Ribose modification

KW - A-form helix

KW - Melting temperature

KW - RNA interference

KW - Stability

KW - siRNA

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DO - 10.1007/s10529-008-9776-4

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Improved serum stability and biophysical properties of siRNAs following chemical modifications

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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