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A screen of chemica...
A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects
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Bramsen, Jesper B. (författare)
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Pakula, Malgorzata M. (författare)
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Hansen, Thomas B. (författare)
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Bus, Claus (författare)
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Langkjaer, Niels (författare)
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Odadzic, Dalibor (författare)
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Smicius, Romualdas (författare)
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Wengel, Suzy L. (författare)
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- Chattopadhyaya, Jyoti (författare)
- Uppsala universitet,Bioorganisk kemi
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Engels, Joachim W. (författare)
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Herdewijn, Piet (författare)
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Wengel, Jesper (författare)
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Kjems, Jorgen (författare)
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(creator_code:org_t)
- 2010-05-07
- 2010
- Engelska.
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 38:17, s. 5761-5773
- Relaterad länk:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene function in mammalian cells yet trigger unintended gene silencing due to their inherent miRNA-like behavior. Such off-target effects are primarily mediated by the sequence-specific interaction between the siRNA seed regions (position 2-8 of either siRNA strand counting from the 5'-end) and complementary sequences in the 3'UTR of (off-) targets. It was previously shown that chemical modification of siRNAs can reduce off-targeting but only very few modifications have been tested leaving more to be identified. Here we developed a luciferase reporter-based assay suitable to monitor siRNA off-targeting in a high throughput manner using stable cell lines. We investigated the impact of chemically modifying single nucleotide positions within the siRNA seed on siRNA function and off-targeting using 10 different types of chemical modifications, three different target sequences and three siRNA concentrations. We found several differently modified siRNAs to exercise reduced off-targeting yet incorporation of the strongly destabilizing unlocked nucleic acid (UNA) modification into position 7 of the siRNA most potently reduced off-targeting for all tested sequences. Notably, such position-specific destabilization of siRNA-target interactions did not significantly reduce siRNA potency and is therefore well suited for future siRNA designs especially for applications in vivo where siRNA concentrations, expectedly, will be low.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Nyckelord
- Biology
- Biologi
- Chemistry
- Kemi
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- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Bramsen, Jesper ...
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Pakula, Malgorza ...
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Hansen, Thomas B ...
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Bus, Claus
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Langkjaer, Niels
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Odadzic, Dalibor
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visa fler...
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Smicius, Romuald ...
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Wengel, Suzy L.
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Chattopadhyaya, ...
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Engels, Joachim ...
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Herdewijn, Piet
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Wengel, Jesper
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Kjems, Jorgen
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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- NATURVETENSKAP
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NATURVETENSKAP
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och Kemi
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Nucleic Acids Re ...
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Uppsala universitet