Most ebook files are in PDF format, so you can easily read them using various software such as Foxit Reader or directly on the Google Chrome browser.
Some ebook files are released by publishers in other formats such as .awz, .mobi, .epub, .fb2, etc. You may need to install specific software to read these formats on mobile/PC, such as Calibre.
Please read the tutorial at this link: https://ebookbell.com/faq
We offer FREE conversion to the popular formats you request; however, this may take some time. Therefore, right after payment, please email us, and we will try to provide the service as quickly as possible.
For some exceptional file formats or broken links (if any), please refrain from opening any disputes. Instead, email us first, and we will try to assist within a maximum of 6 hours.
EbookBell Team
4.4
72 reviewsEpigenetic editing is a promising strategy for modifying gene expression while avoiding the permanent alterations and potential genotoxicity of genome-editing technologies. Here we designed optimized epigenetic regulators (EpiRegs) by testing combinations of transcription activator-like efector (TALE)-based and catalytically deactivated Cas9 (dCas9)-based epigenetic modifcation efectors and fusion protein structures. TALE-based EpiReg (EpiReg-T) achieved a fnal efciency of 98% in mice, surpassing the initial dCas9-based efciency of 64%. We demonstrated the approach in macaques by introducing DNA methylation and histone modifcations to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) expression, thereby lowering low-density lipoprotein cholesterol levels. A single dose of EpiReg-T delivered with lipid nanoparticles achieved efcient (>90%) and long-lasting (343 days) silencing of PCSK9 in the liver. Integrative multiomic analyses revealed minimal of-target efects in EpiReg-T-treated monkeys, mice and human-derived cells. EpiReg can be redirected to other genes by reengineering the DNA-binding domain. Our fndings represent a step toward the clinical application of epigenetic editing for the treatment of human diseases.
