Improved silencing properties using small internally segmented interfering RNAs

J. B. Bramsen, M. B. Laursen, C. K. Damgaard, Suzy Willsen Lena, B. Ravindra Babu, Jesper Wengel, Jørgen Kjems

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Resumé

RNA interference is mediated by small interfering RNAs (siRNAs) that upon incorporation into the RNA-induced silencing complex (RISC) can target complementary mRNA for degradation. Standard siRNA design usually feature a 19–27 base pair contiguous double-stranded region that is believed to be important for RISC incorporation. Here, we describe a novel siRNA design composed of an intact antisense strand complemented with two shorter 10–12 nt sense strands. This three-stranded construct, termed small internally segmented interfering RNA (sisiRNA), is highly functional demonstrating that an intact sense strand is not a prerequisite for RNA interference. Moreover, when using the sisiRNA design only the antisense strand is functional in activated RISC thereby completely eliminating unintended mRNA targeting by the sense strand. Interestingly, the sisiRNA design supports the function of chemically modified antisense strands, which are non-functional within the context of standard siRNA designs. This suggests that the sisiRNA design has a clear potential of improving the pharmacokinetic properties of siRNA in vivo .

OriginalsprogEngelsk
TidsskriftNucleic Acids Research
Vol/bind35
Udgave nummer17
Sider (fra-til)5886-5897
ISSN0305-1048
DOI
StatusUdgivet - 2007

Fingeraftryk

Small Interfering RNA
RNA
RNA Interference
Base Pairing
Pharmacokinetics
Messenger RNA

Citer dette

Bramsen, J. B., Laursen, M. B., Damgaard, C. K., Lena, S. W., Babu, B. R., Wengel, J., & Kjems, J. (2007). Improved silencing properties using small internally segmented interfering RNAs. Nucleic Acids Research, 35(17), 5886-5897. https://doi.org/10.1093/nar/gkm548
Bramsen, J. B. ; Laursen, M. B. ; Damgaard, C. K. ; Lena, Suzy Willsen ; Babu, B. Ravindra ; Wengel, Jesper ; Kjems, Jørgen. / Improved silencing properties using small internally segmented interfering RNAs. I: Nucleic Acids Research. 2007 ; Bind 35, Nr. 17. s. 5886-5897.
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title = "Improved silencing properties using small internally segmented interfering RNAs",
abstract = "RNA interference is mediated by small interfering RNAs (siRNAs) that upon incorporation into the RNA-induced silencing complex (RISC) can target complementary mRNA for degradation. Standard siRNA design usually feature a 19–27 base pair contiguous double-stranded region that is believed to be important for RISC incorporation. Here, we describe a novel siRNA design composed of an intact antisense strand complemented with two shorter 10–12 nt sense strands. This three-stranded construct, termed small internally segmented interfering RNA (sisiRNA), is highly functional demonstrating that an intact sense strand is not a prerequisite for RNA interference. Moreover, when using the sisiRNA design only the antisense strand is functional in activated RISC thereby completely eliminating unintended mRNA targeting by the sense strand. Interestingly, the sisiRNA design supports the function of chemically modified antisense strands, which are non-functional within the context of standard siRNA designs. This suggests that the sisiRNA design has a clear potential of improving the pharmacokinetic properties of siRNA in vivo .",
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Bramsen, JB, Laursen, MB, Damgaard, CK, Lena, SW, Babu, BR, Wengel, J & Kjems, J 2007, 'Improved silencing properties using small internally segmented interfering RNAs', Nucleic Acids Research, bind 35, nr. 17, s. 5886-5897. https://doi.org/10.1093/nar/gkm548

Improved silencing properties using small internally segmented interfering RNAs. / Bramsen, J. B.; Laursen, M. B.; Damgaard, C. K.; Lena, Suzy Willsen; Babu, B. Ravindra; Wengel, Jesper; Kjems, Jørgen.

I: Nucleic Acids Research, Bind 35, Nr. 17, 2007, s. 5886-5897.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Improved silencing properties using small internally segmented interfering RNAs

AU - Bramsen, J. B.

AU - Laursen, M. B.

AU - Damgaard, C. K.

AU - Lena, Suzy Willsen

AU - Babu, B. Ravindra

AU - Wengel, Jesper

AU - Kjems, Jørgen

PY - 2007

Y1 - 2007

N2 - RNA interference is mediated by small interfering RNAs (siRNAs) that upon incorporation into the RNA-induced silencing complex (RISC) can target complementary mRNA for degradation. Standard siRNA design usually feature a 19–27 base pair contiguous double-stranded region that is believed to be important for RISC incorporation. Here, we describe a novel siRNA design composed of an intact antisense strand complemented with two shorter 10–12 nt sense strands. This three-stranded construct, termed small internally segmented interfering RNA (sisiRNA), is highly functional demonstrating that an intact sense strand is not a prerequisite for RNA interference. Moreover, when using the sisiRNA design only the antisense strand is functional in activated RISC thereby completely eliminating unintended mRNA targeting by the sense strand. Interestingly, the sisiRNA design supports the function of chemically modified antisense strands, which are non-functional within the context of standard siRNA designs. This suggests that the sisiRNA design has a clear potential of improving the pharmacokinetic properties of siRNA in vivo .

AB - RNA interference is mediated by small interfering RNAs (siRNAs) that upon incorporation into the RNA-induced silencing complex (RISC) can target complementary mRNA for degradation. Standard siRNA design usually feature a 19–27 base pair contiguous double-stranded region that is believed to be important for RISC incorporation. Here, we describe a novel siRNA design composed of an intact antisense strand complemented with two shorter 10–12 nt sense strands. This three-stranded construct, termed small internally segmented interfering RNA (sisiRNA), is highly functional demonstrating that an intact sense strand is not a prerequisite for RNA interference. Moreover, when using the sisiRNA design only the antisense strand is functional in activated RISC thereby completely eliminating unintended mRNA targeting by the sense strand. Interestingly, the sisiRNA design supports the function of chemically modified antisense strands, which are non-functional within the context of standard siRNA designs. This suggests that the sisiRNA design has a clear potential of improving the pharmacokinetic properties of siRNA in vivo .

U2 - 10.1093/nar/gkm548

DO - 10.1093/nar/gkm548

M3 - Journal article

VL - 35

SP - 5886

EP - 5897

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 17

ER -