Chemical modification patterns compatible with high potency dicer-substrate small interfering RNAs

Michael A. Collingwood; Scott D. Rose; Lingyan Huang; Chris Hillier; Mohammad Amarzguioui; Merete T. Wiiger; Harris S. Soifer; John J. Rossi; Mark A. Behlke

doi:10.1089/oli.2008.0123

Chemical modification patterns compatible with high potency dicer-substrate small interfering RNAs

Michael A. Collingwood, Scott D. Rose, Lingyan Huang, Chris Hillier, Mohammad Amarzguioui, Merete T. Wiiger, Harris S. Soifer, John J. Rossi, Mark A. Behlke

Biological and Biomedical Sciences

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

76 Citations (Scopus)

Abstract

Dicer-substrate small interfering RNAs (DsiRNAs) are synthetic RNA duplexes that are processed by Dicer into 21-mer species and show improved potency as triggers of RNA interference, particularly when used at low dose. Chemical modification patterns that are compatible with high potency 21-mer small interfering RNAs have been reported by several groups. However, modification patterns have not been studied for Dicer-substrate duplexes. We therefore synthesized a series of chemically modified 27-mer DsiRNAs and correlated modification patterns with functional potency. Some modification patterns profoundly reduced function although other patterns maintained high potency. Effects of sequence context were observed, where the relative potency of modification patterns varied between sites.

Original language	English
Pages (from-to)	187-200
Number of pages	14
Journal	Oligonucleotides
Volume	18
Issue number	2
DOIs	https://doi.org/10.1089/oli.2008.0123
Publication status	Published - 1 Jun 2008

Keywords

DsiRNAs
RNA
modification patterns

Documents and Links

10.1089/oli.2008.0123

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title = "Chemical modification patterns compatible with high potency dicer-substrate small interfering RNAs",

abstract = "Dicer-substrate small interfering RNAs (DsiRNAs) are synthetic RNA duplexes that are processed by Dicer into 21-mer species and show improved potency as triggers of RNA interference, particularly when used at low dose. Chemical modification patterns that are compatible with high potency 21-mer small interfering RNAs have been reported by several groups. However, modification patterns have not been studied for Dicer-substrate duplexes. We therefore synthesized a series of chemically modified 27-mer DsiRNAs and correlated modification patterns with functional potency. Some modification patterns profoundly reduced function although other patterns maintained high potency. Effects of sequence context were observed, where the relative potency of modification patterns varied between sites.",

keywords = "DsiRNAs, RNA, modification patterns",

author = "Collingwood, {Michael A.} and Rose, {Scott D.} and Lingyan Huang and Chris Hillier and Mohammad Amarzguioui and Wiiger, {Merete T.} and Soifer, {Harris S.} and Rossi, {John J.} and Behlke, {Mark A.}",

note = "Originally published in: Oligonucleotides (2008), 18 (2), pp.187-200.",

year = "2008",

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doi = "10.1089/oli.2008.0123",

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T1 - Chemical modification patterns compatible with high potency dicer-substrate small interfering RNAs

AU - Collingwood, Michael A.

AU - Rose, Scott D.

AU - Huang, Lingyan

AU - Hillier, Chris

AU - Amarzguioui, Mohammad

AU - Wiiger, Merete T.

AU - Soifer, Harris S.

AU - Rossi, John J.

AU - Behlke, Mark A.

N1 - Originally published in: Oligonucleotides (2008), 18 (2), pp.187-200.

PY - 2008/6/1

Y1 - 2008/6/1

N2 - Dicer-substrate small interfering RNAs (DsiRNAs) are synthetic RNA duplexes that are processed by Dicer into 21-mer species and show improved potency as triggers of RNA interference, particularly when used at low dose. Chemical modification patterns that are compatible with high potency 21-mer small interfering RNAs have been reported by several groups. However, modification patterns have not been studied for Dicer-substrate duplexes. We therefore synthesized a series of chemically modified 27-mer DsiRNAs and correlated modification patterns with functional potency. Some modification patterns profoundly reduced function although other patterns maintained high potency. Effects of sequence context were observed, where the relative potency of modification patterns varied between sites.

AB - Dicer-substrate small interfering RNAs (DsiRNAs) are synthetic RNA duplexes that are processed by Dicer into 21-mer species and show improved potency as triggers of RNA interference, particularly when used at low dose. Chemical modification patterns that are compatible with high potency 21-mer small interfering RNAs have been reported by several groups. However, modification patterns have not been studied for Dicer-substrate duplexes. We therefore synthesized a series of chemically modified 27-mer DsiRNAs and correlated modification patterns with functional potency. Some modification patterns profoundly reduced function although other patterns maintained high potency. Effects of sequence context were observed, where the relative potency of modification patterns varied between sites.

KW - DsiRNAs

KW - RNA

KW - modification patterns

U2 - 10.1089/oli.2008.0123

DO - 10.1089/oli.2008.0123

M3 - Article

VL - 18

SP - 187

EP - 200

JO - Oligonucleotides

JF - Oligonucleotides

SN - 1545-4576

IS - 2

ER -

Chemical modification patterns compatible with high potency dicer-substrate small interfering RNAs

Abstract

Keywords

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