Academic Journal
MicroRNA-like off-target transcript regulation by siRNAs is species specific
| العنوان: | MicroRNA-like off-target transcript regulation by siRNAs is species specific |
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| المؤلفون: | Burchard, Julja, Jackson, Aimee L., Malkov, Vladislav, Needham, Rachel H.V., Tan, Yejun, Bartz, Steven R., Dai, Hongyue, Sachs, Alan B., Linsley, Peter S. |
| بيانات النشر: | Cold Spring Harbor Laboratory Press |
| سنة النشر: | 2009 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | ARTICLE |
| الوصف: | siRNAs mediate sequence-specific gene silencing in cultured mammalian cells but also silence unintended transcripts. Many siRNA off-target transcripts match the guide-strand “seed region,” similar to the way microRNAs match their target sites. The extent to which this seed-matched, microRNA-like, off-target silencing affects the specificity of therapeutic siRNAs in vivo is currently unknown. Here, we compare microRNA-like off-target regulations in mouse liver in vivo with those seen in cell culture for a series of therapeutic candidate siRNAs targeting Apolipoprotein B ( APOB ). Each siRNA triggered regulation of consistent microRNA-like off-target transcripts in mouse livers and in cultured mouse liver tumor cells. In contrast, there was only random overlap between microRNA-like off-target transcripts from cultured human and mouse liver tumor cells. Therefore, siRNA therapeutics may trigger microRNA-like silencing of many unintended targets in vivo, and the potential toxicities caused by these off-target gene regulations cannot be accurately assessed in rodent models. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://rnajournal.cshlp.org/cgi/content/short/15/2/308; http://dx.doi.org/10.1261/rna.1326809 |
| DOI: | 10.1261/rna.1326809 |
| الاتاحة: | http://rnajournal.cshlp.org/cgi/content/short/15/2/308 https://doi.org/10.1261/rna.1326809 |
| Rights: | Copyright (C) 2009, RNA Society |
| رقم الانضمام: | edsbas.4DC0D7E5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1261/rna.1326809 |
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