SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:DiVA.org:uu-134673"
 

Search: onr:"swepub:oai:DiVA.org:uu-134673" > A screen of chemica...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects

Bramsen, Jesper B. (author)
Pakula, Malgorzata M. (author)
Hansen, Thomas B. (author)
show more...
Bus, Claus (author)
Langkjaer, Niels (author)
Odadzic, Dalibor (author)
Smicius, Romualdas (author)
Wengel, Suzy L. (author)
Chattopadhyaya, Jyoti (author)
Uppsala universitet,Bioorganisk kemi
Engels, Joachim W. (author)
Herdewijn, Piet (author)
Wengel, Jesper (author)
Kjems, Jorgen (author)
show less...
 (creator_code:org_t)
2010-05-07
2010
English.
In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 38:17, s. 5761-5773
Related links:
https://academic.oup...
show more...
https://urn.kb.se/re...
https://doi.org/10.1...
show less...
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • 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.

Subject headings

NATURVETENSKAP  -- Biologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences (hsv//eng)
NATURVETENSKAP  -- Kemi (hsv//swe)
NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

Keyword

Biology
Biologi
Chemistry
Kemi

Publication and Content Type

ref (subject category)
art (subject category)

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view