Base-edited cynomolgus monkeys mimic core symptoms of STXBP1 encephalopathy

Lu, Zongyang; He, Siting; Jiang, Jiansheng; Zhuang, Ling; Wang, Yan; Yang, Guang; Jiang, Xiaoyu; Nie, Yanhong; Fu, Jiqiang; Zhang, Xiaolin; Lu, Yong; Bian, Xinyan; Chang, Hung-Chun; Xiong, Zhi‐Qi; Huang, Xingxu; Liu, Zhen; Sun, Qiang

doi:10.1016/j.ymthe.2022.03.001

Cited by 13 publications

(8 citation statements)

References 66 publications

(83 reference statements)

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“…It has been revealed that the AMP-activated protein kinase (AMPK) component PRKAA2 is linked to adverse survival outcomes in both EC [25] and CRC [26]. STXBP1 encodes a syntaxinbinding protein that modulates the release of neurotransmitters [27]. In lung cancer, STXBP1 was found to be down-regulated but was identified as a prognosis-related gene in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients [28,29].…”

Section: Discussionmentioning

confidence: 99%

Identification of an immune-related metabolic gene signature to predict possible prognosis in endometrial cancer and reveals immune landscape feature

2023

European Journal of Gynaecological Oncology

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The immunotherapy of endometrial cancer (EC) has gradually attracted attention and metabolic reprogramming is associate with tumor immune infiltration. Our goal was to use proteome analysis to examine the role of immune-related metabolic genes (IRMGs) in EC. Data-independent acquisition mass spectrometry (DIA-MS) was performed on 20 EC patients, consisting of 10 high-grade and 10 low-grade cancer tissues. IRMGs were screened using Spearman correlation, and an immune-related metabolic prognosis signature (IRMPS) was constructed based on the Cancer Genome Atlas-Uterine Corpus Endometrioid Carcinoma (TCGA-UCEC) cohort using the least absolute shrinkage and selection operator (LASSO) regression analysis. We also investigated differences between different risk groups in terms of prognostic value, clinical potency, immune characteristics and therapy response. In total, 285 differentially expressed genes (DEGs) were acquired via DIA-MS. Subsequently, metabolic-DEGs and immune-DEGs were analyzed by Spearman correlation to identify 41 IRMGs. Finally, seven IRMGs, including NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 2 (NDUFA2), AMPK-alpha2 (PRKAA2), syntaxin binding protein 1 (STXBP1), NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 9 (NDUFB9), ribosomal protein S27-like (RPS27L), lysolecithin acyltransferase 2 (LPCAT2) and uridine monophosphate synthetase (UMPS) were identified to establish a prognosis signature. The risk score was determined as an independent prognostic indicator, and patients in the IRMPS-high group was strong linked with adverse prognosis for EC. Additionally, IRMPS was closely related with tumor immune infiltration. Notably, the IRMPS-low group had better immune checkpoint inhibitors (ICI) treatment response and more sensitive to chemotherapy drugs. In conclusion, IRMPS can serve as a precise prognostic tool to guide the personalized treatment of EC patients.

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Section: Discussionmentioning

confidence: 99%

Identification of an immune-related metabolic gene signature to predict possible prognosis in endometrial cancer and reveals immune landscape feature

2023

European Journal of Gynaecological Oncology

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“…However, at the writing of this review, it is critical to point out that none of these studies have been published, a caveat that is critical given the high and sometimes unrealistic expectations for novel treatments. Gene therapies are under development for several genetic epilepsies, though it is still uncertain as to how these novel approaches will be delivered safely to the central nervous system, and the robustness of an effect they might have [51].…”

Section: Progress In Precision Medicinementioning

confidence: 99%

The current landscape of epilepsy genetics: where are we, and where are we going?

Ruggiero

Xian

Helbig

2023

Current Opinion in Neurology

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Purpose of reviewIn this review, we aim to analyse the progress in understanding the genetic basis of the epilepsies, as well as ongoing efforts to define the increasingly diverse and novel presentations, phenotypes and divergences from the expected that have continually characterized the field.Recent findingsA genetic workup is now considered to be standard of care for individuals with an unexplained epilepsy, due to mounting evidence that genetic diagnoses significantly influence treatment choices, prognostication, community support, and increasingly, access to clinical trials. As more individuals with epilepsy are tested, novel presentations of known epilepsy genes are being discovered, and more individuals with self-limited epilepsy are able to attain genetic diagnoses. In addition, new genes causative of epilepsy are being uncovered through both traditional and novel methods, including large international data-sharing collaborations and massive sequencing efforts as well as computational methods and analyses driven by the Human Phenotype Ontology (HPO).SummaryNew approaches to gene discovery and characterization are advancing rapidly our understanding of the genetic and phenotypic architecture of the epilepsies. This review highlights relevant and groundbreaking studies published recently that have pushed forward the field of epilepsy genetics.

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“…Numerous studies have demonstrated the ability of BEs to correct pathogenic mutations underlying various human genetic diseases, including Duchenne muscular dystrophy ( 116 ), metabolic liver diseases ( 117 , 118 ), hereditary deafness ( 64 ), progeria ( 23 ), Marfan syndrome ( 119 ), sickle cell disease ( 120 ), β-thalassemia ( 121 ), among others. Efficient modeling of pathogenic point mutations using BEs has also been performed in cultured human primary cells ( 122 ), embryos ( 123 , 124 ), and various organisms, including mice ( 125 ), rabbits ( 102 ), pigs ( 126 ), and non-human primates ( 127 – 129 ). In addition to modeling or correcting human pathogenic point mutations, BEs can be used to regulate gene expression in a more precise manner.…”

Section: Gene Editing Systems Mediate Efficient and Precise Genome Ed...mentioning

confidence: 99%

Advances in CRISPR/Cas gene therapy for inborn errors of immunity

Liu

et al. 2023

Front. Immunol.

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Inborn errors of immunity (IEIs) are a group of inherited disorders caused by mutations in the protein-coding genes involved in innate and/or adaptive immunity. Hematopoietic stem cell transplantation (HSCT) is a mainstay definitive therapy for many severe IEIs. However, the lack of HLA-matched donors increases the risk of developing severe immunological complications. Gene therapy provides long-term clinical benefits and could be an attractive therapeutic strategy for IEIs. In this review, we describe the development and evolution of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated proteins (Cas) gene-editing systems, including double-strand break (DSB)-based gene editing and DSB-free base editing or prime editing systems. Here, we discuss the advances in and issues associated with CRISPR/Cas gene editing tools and their potential as therapeutic alternatives for IEIs. We also highlight the progress of preclinical studies for the treatment of human genetic diseases, including IEIs, using CRISR/Cas and ongoing clinical trials based on this versatile technology.

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Base-edited cynomolgus monkeys mimic core symptoms of STXBP1 encephalopathy

Cited by 13 publications

References 66 publications

Identification of an immune-related metabolic gene signature to predict possible prognosis in endometrial cancer and reveals immune landscape feature

Identification of an immune-related metabolic gene signature to predict possible prognosis in endometrial cancer and reveals immune landscape feature

The current landscape of epilepsy genetics: where are we, and where are we going?

Advances in CRISPR/Cas gene therapy for inborn errors of immunity

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