Modulating anti-MicroRNA-21 activity and specificity using oligonucleotide derivatives and length optimization

Andres Munoz-Alarcon, Peter Guterstam, Cristian Romero, Mark A. Behlke, Kim A. Lennox, Jesper Wengel, Samir EL Andaloussi, Ulo Langel

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

MicroRNAs are short, endogenous RNAs that direct posttranscriptional regulation of gene expression vital for many developmental and cellular functions. Implicated in the pathogenesis of several human diseases, this group of RNAs provides interesting targets for therapeutic intervention. Anti-microRNA oligonucleotides constitute a class of synthetic antisense oligonucleotides used to interfere with microRNAs. In this study, we investigate the effects of chemical modifications and truncations on activity and specificity of anti-microRNA oligonucleotides targeting microRNA-21. We observed an increased activity but reduced specificity when incorporating locked nucleic acid monomers, whereas the opposite was observed when introducing unlocked nucleic acid monomers. Our data suggest that phosphorothioate anti-microRNA oligonucleotides yield a greater activity than their phosphodiester counterparts and that a moderate truncation of the anti-microRNA oligonucleotide improves specificity without significantly losing activity. These results provide useful insights for design of anti-microRNA oligonucleotides to achieve both high activity as well as efficient mismatch discrimination.

OriginalsprogEngelsk
TidsskriftISRN Pharmaceutics
Vol/bind2012
Udgave nummerID 407154
Sider (fra-til)1-7
Antal sider7
DOI
StatusUdgivet - 2012

Fingeraftryk

MicroRNAs
RNA
Nucleic Acids

Citer dette

Munoz-Alarcon, A., Guterstam, P., Romero, C., Behlke, M. A., Lennox, K. A., Wengel, J., ... Langel, U. (2012). Modulating anti-MicroRNA-21 activity and specificity using oligonucleotide derivatives and length optimization. ISRN Pharmaceutics , 2012(ID 407154), 1-7. https://doi.org/10.5402/2012/407154
Munoz-Alarcon, Andres ; Guterstam, Peter ; Romero, Cristian ; Behlke, Mark A. ; Lennox, Kim A. ; Wengel, Jesper ; EL Andaloussi, Samir ; Langel, Ulo. / Modulating anti-MicroRNA-21 activity and specificity using oligonucleotide derivatives and length optimization. I: ISRN Pharmaceutics . 2012 ; Bind 2012, Nr. ID 407154. s. 1-7.
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abstract = "MicroRNAs are short, endogenous RNAs that direct posttranscriptional regulation of gene expression vital for many developmental and cellular functions. Implicated in the pathogenesis of several human diseases, this group of RNAs provides interesting targets for therapeutic intervention. Anti-microRNA oligonucleotides constitute a class of synthetic antisense oligonucleotides used to interfere with microRNAs. In this study, we investigate the effects of chemical modifications and truncations on activity and specificity of anti-microRNA oligonucleotides targeting microRNA-21. We observed an increased activity but reduced specificity when incorporating locked nucleic acid monomers, whereas the opposite was observed when introducing unlocked nucleic acid monomers. Our data suggest that phosphorothioate anti-microRNA oligonucleotides yield a greater activity than their phosphodiester counterparts and that a moderate truncation of the anti-microRNA oligonucleotide improves specificity without significantly losing activity. These results provide useful insights for design of anti-microRNA oligonucleotides to achieve both high activity as well as efficient mismatch discrimination.",
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Munoz-Alarcon, A, Guterstam, P, Romero, C, Behlke, MA, Lennox, KA, Wengel, J, EL Andaloussi, S & Langel, U 2012, 'Modulating anti-MicroRNA-21 activity and specificity using oligonucleotide derivatives and length optimization', ISRN Pharmaceutics , bind 2012, nr. ID 407154, s. 1-7. https://doi.org/10.5402/2012/407154

Modulating anti-MicroRNA-21 activity and specificity using oligonucleotide derivatives and length optimization. / Munoz-Alarcon, Andres; Guterstam, Peter; Romero, Cristian; Behlke, Mark A.; Lennox, Kim A.; Wengel, Jesper; EL Andaloussi, Samir; Langel, Ulo.

I: ISRN Pharmaceutics , Bind 2012, Nr. ID 407154, 2012, s. 1-7.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Modulating anti-MicroRNA-21 activity and specificity using oligonucleotide derivatives and length optimization

AU - Munoz-Alarcon, Andres

AU - Guterstam, Peter

AU - Romero, Cristian

AU - Behlke, Mark A.

AU - Lennox, Kim A.

AU - Wengel, Jesper

AU - EL Andaloussi, Samir

AU - Langel, Ulo

PY - 2012

Y1 - 2012

N2 - MicroRNAs are short, endogenous RNAs that direct posttranscriptional regulation of gene expression vital for many developmental and cellular functions. Implicated in the pathogenesis of several human diseases, this group of RNAs provides interesting targets for therapeutic intervention. Anti-microRNA oligonucleotides constitute a class of synthetic antisense oligonucleotides used to interfere with microRNAs. In this study, we investigate the effects of chemical modifications and truncations on activity and specificity of anti-microRNA oligonucleotides targeting microRNA-21. We observed an increased activity but reduced specificity when incorporating locked nucleic acid monomers, whereas the opposite was observed when introducing unlocked nucleic acid monomers. Our data suggest that phosphorothioate anti-microRNA oligonucleotides yield a greater activity than their phosphodiester counterparts and that a moderate truncation of the anti-microRNA oligonucleotide improves specificity without significantly losing activity. These results provide useful insights for design of anti-microRNA oligonucleotides to achieve both high activity as well as efficient mismatch discrimination.

AB - MicroRNAs are short, endogenous RNAs that direct posttranscriptional regulation of gene expression vital for many developmental and cellular functions. Implicated in the pathogenesis of several human diseases, this group of RNAs provides interesting targets for therapeutic intervention. Anti-microRNA oligonucleotides constitute a class of synthetic antisense oligonucleotides used to interfere with microRNAs. In this study, we investigate the effects of chemical modifications and truncations on activity and specificity of anti-microRNA oligonucleotides targeting microRNA-21. We observed an increased activity but reduced specificity when incorporating locked nucleic acid monomers, whereas the opposite was observed when introducing unlocked nucleic acid monomers. Our data suggest that phosphorothioate anti-microRNA oligonucleotides yield a greater activity than their phosphodiester counterparts and that a moderate truncation of the anti-microRNA oligonucleotide improves specificity without significantly losing activity. These results provide useful insights for design of anti-microRNA oligonucleotides to achieve both high activity as well as efficient mismatch discrimination.

U2 - 10.5402/2012/407154

DO - 10.5402/2012/407154

M3 - Journal article

VL - 2012

SP - 1

EP - 7

JO - ISRN Pharmaceutics

JF - ISRN Pharmaceutics

SN - 2090-6153

IS - ID 407154

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