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Superior Silencing by 2′,4′-BNANC-Based Short Antisense Oligonucleotides Compared to 2′,4′-BNALNA-Based Apolipoprotein B Antisense Inhibitors
المؤلفون المشاركون
Yasuhara, Hidenori
Harada-Shiba, Mariko
Obika, Satoshi
Yamamoto, Tsuyoshi
Imanishi, Takeshi
Wada, Fumito
المصدر
العدد
المجلد 2012، العدد 2012 (31 ديسمبر/كانون الأول 2012)، ص ص. 1-7، 7ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2012-09-26
دولة النشر
مصر
عدد الصفحات
7
التخصصات الرئيسية
الملخص EN
The duplex stability with target mRNA and the gene silencing potential of a novel bridged nucleic acid analogue are described.
The analogue, 2′,4′-BNANC antisense oligonucleotides (AONs) ranging from 10- to 20-nt-long, targeted apolipoprotein B.
2′,4′-BNANC was directly compared to its conventional bridged (or locked) nucleic acid (2′,4′-BNA/LNA)-based counterparts.
Melting temperatures of duplexes formed between 2′,4′-BNANC-based antisense oligonucleotides and the target mRNA surpassed those of 2′,4′-BNA/LNA-based counterparts at all lengths.
An in vitro transfection study revealed that when compared to the identical length 2′,4′-BNA/LNA-based counterpart, the corresponding 2′,4′-BNANC-based antisense oligonucleotide showed significantly stronger inhibitory activity.
This inhibitory activity was more pronounced in shorter (13-, 14-, and 16-mer) oligonucleotides.
On the other hand, the 2′,4′-BNANC-based 20-mer AON exhibited the highest affinity but the worst IC50 value, indicating that very high affinity may undermine antisense potency.
These results suggest that the potency of AONs requires a balance between reward term and penalty term.
Balance of these two parameters would depend on affinity, length, and the specific chemistry of the AON, and fine-tuning of this balance could lead to improved potency.
We demonstrate that 2′,4′-BNANC may be a better alternative to conventional 2′,4′-BNA/LNA, even for “short” antisense oligonucleotides, which are attractive in terms of drug-likeness and cost-effective bulk production.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Yamamoto, Tsuyoshi& Yasuhara, Hidenori& Wada, Fumito& Harada-Shiba, Mariko& Imanishi, Takeshi& Obika, Satoshi. 2012. Superior Silencing by 2′,4′-BNANC-Based Short Antisense Oligonucleotides Compared to 2′,4′-BNALNA-Based Apolipoprotein B Antisense Inhibitors. Journal of Nucleic Acids،Vol. 2012, no. 2012, pp.1-7.
https://search.emarefa.net/detail/BIM-492167
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Yamamoto, Tsuyoshi…[et al.]. Superior Silencing by 2′,4′-BNANC-Based Short Antisense Oligonucleotides Compared to 2′,4′-BNALNA-Based Apolipoprotein B Antisense Inhibitors. Journal of Nucleic Acids No. 2012 (2012), pp.1-7.
https://search.emarefa.net/detail/BIM-492167
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Yamamoto, Tsuyoshi& Yasuhara, Hidenori& Wada, Fumito& Harada-Shiba, Mariko& Imanishi, Takeshi& Obika, Satoshi. Superior Silencing by 2′,4′-BNANC-Based Short Antisense Oligonucleotides Compared to 2′,4′-BNALNA-Based Apolipoprotein B Antisense Inhibitors. Journal of Nucleic Acids. 2012. Vol. 2012, no. 2012, pp.1-7.
https://search.emarefa.net/detail/BIM-492167
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-492167
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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