دورية أكاديمية
Design of hypoxia responsive CRISPR-Cas9 for target gene regulation
| العنوان: | Design of hypoxia responsive CRISPR-Cas9 for target gene regulation |
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| المؤلفون: | Yan An, Chandana S. Talwar, Kwang-Hyun Park, Woo-Chan Ahn, Su-Jin Lee, Seong-Ryeong Go, Jin Hwa Cho, Do Yon Kim, Yong-Sam Kim, Sayeon Cho, Jeong-Hoon Kim, Tae-Jip Kim, Eui-Jeon Woo |
| المصدر: | Scientific Reports, Vol 13, Iss 1, Pp 1-14 (2023) |
| بيانات النشر: | Nature Portfolio, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract The CRISPR–Cas9 system is a widely used gene-editing tool, offering unprecedented opportunities for treating various diseases. Controlling Cas9/dCas9 activity at specific location and time to avoid undesirable effects is very important. Here, we report a conditionally active CRISPR–Cas9 system that regulates target gene expression upon sensing cellular environmental change. We conjugated the oxygen-sensing transcription activation domain (TAD) of hypoxia-inducing factor (HIF-1α) with the Cas9/dCas9 protein. The Cas9-TAD conjugate significantly increased endogenous target gene cleavage under hypoxic conditions compared with that under normoxic conditions, whereas the dCas9-TAD conjugate upregulated endogenous gene transcription. Furthermore, the conjugate system effectively downregulated the expression of SNAIL, an essential gene in cancer metastasis, and upregulated the expression of the tumour-related genes HNF4 and NEUROD1 under hypoxic conditions. Since hypoxia is closely associated with cancer, the hypoxia-dependent Cas9/dCas9 system is a novel addition to the molecular tool kit that functions in response to cellular signals and has potential application for gene therapeutics. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-023-43711-9 |
| URL الوصول: | https://doaj.org/article/85522f94b0f74edaa6d4e771cc80a4e3 |
| رقم الأكسشن: | edsdoj.85522f94b0f74edaa6d4e771cc80a4e3 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-023-43711-9 |