کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8306099 1538457 2016 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
CRISPR/Cas9-mediated target validation of the splicing inhibitor Pladienolide B
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
CRISPR/Cas9-mediated target validation of the splicing inhibitor Pladienolide B
چکیده انگلیسی
CRISPR/Cas9 system confers molecular immunity in archeal and bacterial species against invading foreign nucleic acids. CRISPR/Cas9 system is used for genome engineering applications across diverse eukaryotic species. In this study, we demonstrate the utility of the CRISPR/Cas9 genome engineering system for drug target validation in human cells. Pladienolide B is a natural macrolide with antitumor activities mediated through the inhibition of pre-mRNA splicing. To validate the spliceosomal target of Pladienolide B, we employed the CRSIPR/Cas9 system to introduce targeted mutations in the subunits of the SF3B complex in the HEK293T cells. Our data reveal that targeted mutagenesis of the SF3b1 subunit exhibited higher levels of resistance to Pladienolide B. Therefore, our data validate the spliceosomal target of Pladienolide B and provide a proof of concept on using the CRISPR/Cas9 system for drug target identification and validation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimie Open - Volume 3, December 2016, Pages 72-75
نویسندگان
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