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All types of base conversions allowed by base editors
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Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing
The expanding applications of nonviral genomic medicines in the lung remain restricted by delivery challenges. Here, leveraging a high-throughput platform, we synthesize and screen a combinatorial library of b...
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Genome-wide profiling of prime editor off-target sites in vitro and in vivo using PE-tag
Prime editors have a broad range of potential research and clinical applications. However, methods to delineate their genome-wide editing activities have generally relied on indirect genome-wide editing assess...
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Open AccessMEK1 drives oncogenic signaling and interacts with PARP1 for genomic and metabolic homeostasis in malignant pleural mesothelioma
Malignant pleural mesothelioma (MPM) is a lethal malignancy etiologically caused by asbestos exposure, for which there are few effective treatment options. Although asbestos carcinogenesis is associated with r...
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A split prime editor with untethered reverse transcriptase and circular RNA template
Delivery and optimization of prime editors (PEs) have been hampered by their large size and complexity. Although split versions of genome-editing tools can reduce construct size, they require special engineeri...
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Open AccessGenome-wide detection of CRISPR editing in vivo using GUIDE-tag
Analysis of off-target editing is an important aspect of the development of safe nuclease-based genome editing therapeutics. in vivo assessment of nuclease off-target activity has primarily been indirect (base...
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Open AccessMetabolic synthetic lethality by targeting NOP56 and mTOR in KRAS-mutant lung cancer
Oncogenic KRAS mutations are prevalent in human cancers, but effective treatment of KRAS-mutant malignancies remains a major challenge in the clinic. Increasing evidence suggests that aberrant metabolism plays a ...
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Open AccessMalignant pleural mesothelioma co-opts BCL-XL and autophagy to escape apoptosis
Escape from programmed cell death is a hallmark of cancer. In this study, we investigated the anti-apoptotic mechanisms and explored the therapeutic potential of BCL-2 homology domain-3 (BH3) mimetics in malig...
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Open AccessImproved prime editors enable pathogenic allele correction and cancer modelling in adult mice
Prime editors (PEs) mediate genome modification without utilizing double-stranded DNA breaks or exogenous donor DNA as a template. PEs facilitate nucleotide substitutions or local insertions or deletions withi...
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Open AccessHSP90/AXL/eIF4E-regulated unfolded protein response as an acquired vulnerability in drug-resistant KRAS-mutant lung cancer
Drug resistance and tumor heterogeneity are formidable challenges in cancer medicine, which is particularly relevant for KRAS-mutant cancers, the epitome of malignant tumors recalcitrant to targeted therapy effor...
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mTOR mediates a mechanism of resistance to chemotherapy and defines a rational combination strategy to treat KRAS-mutant lung cancer
Oncogenic KRAS mutations comprise the largest subset of lung cancer defined by genetic alterations, but in the clinic no targeted therapies are available that effectively control mutational KRAS activation. Conse...
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Open AccessIncreased sensitivity to apoptosis upon endoplasmic reticulum stress-induced activation of the unfolded protein response in chemotherapy-resistant malignant pleural mesothelioma
Standard treatment for advanced malignant pleural mesothelioma (MPM) is a cisplatin/pemetrexed (MTA) regimen; however, this is confronted by drug resistance. Proteotoxic stress in the endoplasmic reticulum (ER...
