Abstract：
:Precisely targeted genome editing is highly desired for clinical applications. However, the widely used homology-directed repair (HDR)-based genome editing strategies remain inefficient for certain in vivo applications. We here demonstrate a microhomology-mediated end-joining (MMEJ)-based strategy for precisely targeted gene integration in transfected neurons and hepatocytes in vivo with efficiencies up to 20%, much higher (up to 10 fold) than HDR-based strategy in adult mouse tissues. As a proof of concept of its therapeutic potential, we demonstrate the efficacy of MMEJ-based strategy in correction of Fah mutation and rescue of Fah-/- liver failure mice, offering an efficient approach for precisely targeted gene therapies.
journal_name
EBioMedicinejournal_title
EBioMedicineauthors
Yao X,Wang X,Liu J,Hu X,Shi L,Shen X,Ying W,Sun X,Wang X,Huang P,Yang Hdoi
10.1016/j.ebiom.2017.05.015subject
Has Abstractpub_date
2017-06-01 00:00:00pages
19-26issn
2352-3964pii
S2352-3964(17)30213-Xjournal_volume
20pub_type
杂志文章相关文献
EBioMedicine文献大全abstract：BACKGROUND:Human endogenous retroviruses HERV-W encode a pro-inflammatory protein, named MSRV-Env from its original identification in Multiple Sclerosis. Though not detected in various neurological controls, MSRV-Env was found in patients with chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs). This st...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2016.03.001
更新日期：2016-04-01 00:00:00
abstract：BACKGROUND:Spleen tyrosine kinase (SYK) is frequently upregulated in recurrent ovarian carcinomas, for which effective therapy is urgently needed. SYK phosphorylates several substrates, but their translational implications remain unclear. Here, we show that SYK interacts with EGFR and ERBB2, and directly enhances their...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2019.08.055
更新日期：2019-09-01 00:00:00
abstract：BACKGROUND:High-molecular-weight kininogen is a cofactor of the human contact system, an inflammatory response mechanism that is activated during sepsis. It has been shown that high-molecular-weight kininogen contributes to endotoxemia, but is not critical for local host defense during pneumonia by Gram-negative bacter...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2020.102908
更新日期：2020-08-01 00:00:00
abstract：:Histone deacetylases (HDACs) are enzymes that regulate protein functions by catalyzing the removal of acetyl and acyl groups from lysine residues. They play pivotal roles in governing cell behaviors and are indispensable in numerous biological processes. HDAC11, the last identified and sole member of class IV HDACs, w...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2018.06.025
更新日期：2018-07-01 00:00:00
abstract：BACKGROUND:Cisplatin resistance remains a major clinical obstacle to the successful treatment of non-small cell lung cancer (NSCLC). Scribble contributes to ROS-induced inflammation and cisplatin-elevated toxic reactive oxygen species (ROS) promotes cell death. However, it is unknown whether and how Scribble is involve...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2019.08.057
更新日期：2019-09-01 00:00:00
abstract：BACKGROUND:Half of muscle-invasive bladder cancer patients will relapse with metastatic disease and molecular tests to predict relapse are needed. TP63 has been proposed as a prognostic biomarker in bladder cancer, but reports associating it with clinical outcomes are conflicting. Since TP63 is expressed as multiple is...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2019.11.022
更新日期：2020-01-01 00:00:00
abstract：BACKGROUND:Lipid accumulation has been highlighted in cancer development and progression, but the exact mechanism remains unclear in renal cell carcinoma (RCC). MicroRNAs (miRNAs) have been confirmed to participate in the pathological processes of cancers, including tumour occurrence and inhibition. However, the role a...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2019.102622
更新日期：2020-01-01 00:00:00
abstract：BACKGROUND:To improve the early diagnosis of hepatocellular carcinoma (HCC), more effective diagnostic biomarkers are needed. A combination of biomarkers is reported to distinguish individuals with early-stage HCC from at-risk individuals. METHODS:Participants in this study were recruited from six hospitals in China. ...
journal_title：EBioMedicine
pub_type： 杂志文章,多中心研究
doi：10.1016/j.ebiom.2020.102638
更新日期：2020-02-01 00:00:00
abstract：BACKGROUND:Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2015.05.009
更新日期：2015-05-09 00:00:00
abstract：BACKGROUND:Accelerated telomere shortening may cause cancer via chromosomal instability, making it a potentially useful biomarker. However, publications on blood telomere length (BTL) and cancer are inconsistent. We prospectively examined BTL measures over time and cancer incidence. METHODS:We included 792 Normative A...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2015.04.008
更新日期：2015-04-13 00:00:00
abstract：BACKGROUND:Chronic Hepatitis B (CHB) remains a major problem for global public health. Viral persistence and immune defects are the two major reasons for CHB, and it was hypothesized that based on a transient clearance of serum viral DNA and HBsAg "window stage", active immunization against hepatitis B virus (HBV) migh...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2019.10.043
更新日期：2019-11-01 00:00:00
abstract：:Acute myocardial infarction (AMI) and the heart failure (HF) that often follows are among the leading causes of death and disability worldwide. As such, new treatments are needed to protect the myocardium against the damaging effects of the acute ischaemia and reperfusion injury (IRI) that occurs in AMI, in order to r...
journal_title：EBioMedicine
pub_type： 杂志文章,评审
doi：10.1016/j.ebiom.2020.102884
更新日期：2020-07-01 00:00:00
abstract：:Lung cancer is the most frequent cause of cancer-related death world-wide. Radiotherapy alone or in conjunction with chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patien...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2015.06.013
更新日期：2015-06-19 00:00:00
abstract：BACKGROUND:Robust prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is important for developing individualized treatment plans. This study was conducted to develop and validate a clinically feasible prognostic classifier based on transcriptome-wide gene expression profiles. METHO...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2020.102805
更新日期：2020-11-01 00:00:00
abstract：BACKGROUND:Endothelial dysfunction, characterized by diminished endothelial progenitor cell (EPC) function and flow-mediated vasodilation (FMD), is a clinically significant feature of heart failure (HF). Mesenchymal stem cells (MSCs), which have pro-angiogenic properties, have the potential to restore endothelial funct...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2015.03.020
更新日期：2015-03-28 00:00:00
abstract：BACKGROUND:A tick-borne segmented RNA virus called Jingmen tick virus (JMTV) was recently identified, variants of which were detected in a non-human primate host and fatal patients with Crimean-Congo haemorrhagic fever. We investigated its infectivity and pathogenicity for humans. METHODS:We obtained skin-biopsy, bloo...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2019.04.004
更新日期：2019-05-01 00:00:00
abstract：BACKGROUND:In Western cohorts, the prevalence of incidental findings (IFs) or incidentalome, referring to variants in genes that are unrelated to the patient's primary condition, is between 0.86% and 8.8%. However, data on prevalence and type of IFs in Asian population is lacking. METHODS:In 2 cohorts of individuals w...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2016.01.030
更新日期：2016-02-04 00:00:00
abstract：BACKGROUND:Tissue stem cells (SCs) and cancer cells proliferation is regulated by many common signalling mechanisms. These mechanisms temporally balance proliferation and differentiation events during normal tissue homeostasis and repair. However, the effect of these aberrant signalling mechanisms on the ultimate fate ...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2019.08.053
更新日期：2019-10-01 00:00:00
abstract：:The identification of SYK as a molecular target in B-lineage leukemia/lymphoma cells prompted the development of SYK inhibitors as a new class of anti-cancer drug candidates. Here we report that induction of the SYK gene expression in human cells causes a significant down-regulation of evolutionarily conserved genes a...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2014.10.019
更新日期：2014-11-01 00:00:00
abstract：BACKGROUND:Sepsis involves aberrant immune responses to infection, but the exact nature of this immune dysfunction remains poorly defined. Bacterial endotoxins like lipopolysaccharide (LPS) are potent inducers of inflammation, which has been associated with the pathophysiology of sepsis, but repeated exposure can also ...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2014.10.003
更新日期：2014-11-01 00:00:00
abstract：BACKGROUND:Neurodegenerative diseases are incurable disorders caused by progressive neuronal cell death. Retinitis pigmentosa (RP) is a blinding neurodegenerative disease that results in photoreceptor death and progresses to the loss of the entire retinal network. We previously found that proteomic analysis of the adja...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2020.102636
更新日期：2020-02-01 00:00:00
abstract：BACKGROUND:Intra-tumour heterogeneity in lymphoid malignancies encompasses selection of genetic events and epigenetic regulation of transcriptional programs. Clonal-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tis...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2020.103055
更新日期：2020-11-01 00:00:00
abstract：BACKGROUND:Transcriptional dysregulation drives cancer formation but the underlying mechanisms are still poorly understood. Renal cell carcinoma (RCC) is the most common malignant kidney tumor which canonically activates the hypoxia-inducible transcription factor (HIF) pathway. Despite intensive study, novel therapeuti...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2019.01.063
更新日期：2019-03-01 00:00:00
abstract：:Pyrazinamide remains the only drug in the tuberculosis pharmacopeia to drastically shorten first-line therapy from nine to six months. Due to its unparalleled ability to sterilize non-replicating bacilli and reduce relapse rates, PZA is expected to be irreplaceable in future therapies against tuberculosis. While the m...
journal_title：EBioMedicine
pub_type： 杂志文章,评审
doi：10.1016/j.ebiom.2019.10.014
更新日期：2019-11-01 00:00:00
abstract：:Pericardial tuberculosis (TB) is associated with high therapy failure and high mortality rates. Antibiotics have to penetrate to site of infection at sufficient non-protein bound concentrations, and then enter bacteria to inhibit intracellular biochemical processes. The antibiotic concentrations achieved in pericardia...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2015.09.025
更新日期：2015-09-16 00:00:00
abstract：:Pancreatic ductal adenocarcinoma (PDAC) shows remarkable propensity to metastasize. This predilection to escape from the primary tumor is driven by paracrine and autocrine mechanisms that guide cancer cells through a multi-step process concluding with colonization in distant tissues. Although cell-intrinsic features s...
journal_title：EBioMedicine
pub_type： 杂志文章,评审
doi：10.1016/j.ebiom.2020.102662
更新日期：2020-03-01 00:00:00
abstract：:Cardiovascular diseases (CVDs) are the leading cause of death and a major cause of disability globally. Transcription factor EB (TFEB), as a member of the microphthalmia transcription factor (MITF) family, has been demonstrated to be a master regulator of autophagy and lysosomal biogenesis. Emerging studies suggest th...
journal_title：EBioMedicine
pub_type： 杂志文章,评审
doi：10.1016/j.ebiom.2020.103207
更新日期：2021-01-01 00:00:00
abstract：BACKGROUND:Accumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma. METHODS:The Apcmin/+ mice gavage with phosphate-buffere...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2019.09.021
更新日期：2019-10-01 00:00:00
abstract：:Latently human immunodeficiency virus (HIV)-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR) induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen producti...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2017.07.019
更新日期：2017-09-01 00:00:00
abstract：BACKGROUND:Several studies have reported microRNAs (miRNAs) could regulate the placental development, though the role and mechanism of miRNAs in the development of non-diabetic macrosomia (NDFMS) remains unclear. METHODS:To identify the aberrantly expressed key miRNAs in placenta of NDFMS, we employed a strategy consi...
journal_title：EBioMedicine
pub_type： 杂志文章
doi：10.1016/j.ebiom.2018.11.002
更新日期：2018-12-01 00:00:00
