CD8 T play essential roles in antitumor immune responses. However, immunotherapy has limited clinical efficacy in many solid tumors. Here, we performed an epigenetic-wide CRISPR-Cas9 screen in CD8 T cells directly under cancer immunotherapy setting and found that is a transcriptional repressor implicated in nociceptive neuron development but uncharacterized within immunological contexts.
View Article and Find Full Text PDFEx vivo autologous haematopoietic stem cell (HSC) gene therapy provides a promising treatment option for haematological disorders. However, current methods involve complex processes and chemotherapeutic conditioning, leading to limited accessibility for treatment and major side effects. Here we develop antibody-free targeted lipid nanoparticles (LNPs) for mRNA delivery to HSCs in vivo, enabling efficient base editing of the γ-globin gene (HBG1/2) promoter target in human HSCs to reactivate fetal haemoglobin in derived erythroid cells.
View Article and Find Full Text PDFGlobal routing is an important link in very large scale integration (VLSI) design. As the best model of global routing, X-architecture Steiner minimal tree (XSMT) has a good performance in wire length optimization. XSMT belongs to non-Manhattan structural model, and its construction process cannot be completed in polynomial time, so the generation of XSMT is an NP hard problem.
View Article and Find Full Text PDFFront Bioeng Biotechnol
January 2021
The introduction of multi-gene metabolic pathways is generally the first step for the construction of microbial cell factories and plays an essential role in metabolic engineering and synthetic biology. Here, we developed a "PCR & Go" system for facile integration and assembly of multi-gene pathways into the chromosome of . The core component of the "PCR & Go" system was an expression chassis, where eight promoter/terminator pairs were pre-installed into the yeast chromosome and PCR amplified gene fragments could be inserted directly for functional expression.
View Article and Find Full Text PDFThis study aimed to evaluate the role of FRT in ROS/DNA regulation with or without PARP-1 in radiation-injured thymus cells. The administration of FRT to PARP-1-/- (KO) mice demonstrated that FRT significantly increased the viability of thymus cells and decreased their rate of apoptosis through PARP-1. Radiation increased the levels of ROS, γ-H2AX and 53BP1, and induced DNA double strand breaks.
View Article and Find Full Text PDFACS Synth Biol
September 2020
Combinatorial metabolic engineering has been widely established for the development of efficient microbial cell factories to produce the products of interest by precisely regulating the expression levels of multiple genes simultaneously. Here, we report a novel multifunctional CRISPR system that enables simultaneous gene activation, repression, and editing (CRISPR-ARE) with a single Cas9-VPR protein for combinatorial metabolic engineering applications in . Via gRNA engineering, we achieved orthogonal transcriptional regulations and genome editing using the nuclease active Cas9-VPR fusion protein, individually or in a combinatorial manner.
View Article and Find Full Text PDFThe present study evaluated the protective effect of the natural compound flavonoids of Rosa roxburghii Tratt (FRT) against γ-radiation-induced apoptosis and inflammation in mouse thymus cells in vivo and in vitro. Thymus cells and mice were exposed to Co γ-ray at a dose of 6 Gy. The radiation treatment induced significant cell apoptosis and inflammation.
View Article and Find Full Text PDFTrop J Pharm Res
January 2018
Purpose: To perform a qualitative and quantitative analysis of catechin and quercetin in flavonoids extracted from Rosa roxburghii Tratt.
Methods: Total flavonoids were determined using ultraviolet spectrophotometry (UV) at 500 nm. The optimal gradient program started with 15 % methanol and was kept within a period of 0 - 20 min, while 25 % methanol was kept within 20 - 33 min.
J Cell Biochem
April 2018
It was found that the expression level of miR-147a was significantly increased and the pathway of PI3K/AKT was dramatically inhibited after radiation. In view of the relationship between miRNA and target genes, we put forward the question, what is the relationship between PI3K/AKT and miR-147a? In order to find the answer to the question, we used bioinformatics techniques to analyze the relationship between miR-147 (a or b) and PI3K/AKT signaling pathway. miR-147a overexpression plasmid and PDPK1 3'UTR luciferase reporter gene plasmid were constructed.
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