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中国科学:生命科学（英文版）
中国科学:生命科学（英文版）

周光召

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中国科学:生命科学（英文版）/Journal Science China(Life Sciences)CSCDCSTPCDSCI
查看更多>>《中国科学》是中国科学院主办、中国科学杂志社出版的自然科学专业性学术刊物。《中国科学》任务是反映中国自然科学各学科中的最新科研成果，以促进国内外的学术交流。《中国科学》以论文形式报道中国基础研究和应用研究方面具有创造性的、高水平的和有重要意义的科研成果。在国际学术界，《中国科学》作为代表中国最高水平的学术刊物也受到高度重视。国际上最具有权威的检索刊物SCI，多年来一直收录《中国科学》的论文。1999年《中国科学》夺得国家期刊奖的第一名。
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    Genome editing technology and medical applications

    Liren WangBin ZhouDali Li
    2537-2539页
      原文链接:
    • 万方数据
    • 维普

    AAV-mediated gene therapies by miniature gene editing tools

    Xiangfeng KongTong LiHui Yang
    2540-2553页
    查看更多>>摘要：The advent of CRISPR-Cas has revolutionized precise gene editing.While pioneering CRISPR nucleases like Cas9 and Cas12 generate targeted DNA double-strand breaks(DSB)for knockout or homology-directed repair,next generation CRISPR technologies enable gene editing without DNA DSB.Base editors directly convert bases,prime editors make diverse alterations,and dead Cas-regulator fusions allow nuanced control of gene expression,avoiding potentially risks like translocations.Meanwhile,the discovery of diminutive Cas12 orthologs and Obligate Mobile Element-Guided Activity(OMEGA)nucleases has overcome cargo limitations of adeno-associated viral vectors,ex-panding prospects for in vivo therapeutic delivery.Here,we review the ever-evolving landscape of cutting-edge gene editing tools,focusing on miniature Cas12 orthologs and OMEGA effectors amenable to single AAV packaging.We also summarize CRISPR therapies delivered using AAV vectors,discuss challenges such as efficiency and specificity,and look to the future of this transformative field of in vivo gene editing enabled by AAV vectors delivery.
      原文链接:
    • 万方数据
    • 维普

    CRISPR-based genetic screens advance cancer immunology

    Yuanfang CaoXueting LiYumu PanHuahe Wang...
    2554-2562页
    查看更多>>摘要：CRISPR technologies have revolutionized research areas ranging from fundamental science to translational medicine.CRISPR-based genetic screens offer a powerful platform for unbiased screening in various fields,such as cancer immunology.Immune checkpoint blockade(ICB)therapy has been shown to strongly affect cancer treatment.However,the currently available ICBs are limited and do not work in all cancer patients.Pooled CRISPR screens enable the identification of previously unknown immune regulators that can regulate T-cell activation,cytotoxicity,persistence,infiltration into tumors,cytokine secretion,memory formation,T-cell metabolism,and CD4+T-cell differentiation.These novel targets can be developed as new immunotherapies or used with the current ICBs as new combination therapies that may yield synergistic efficacy.Here,we review the progress made in the development of CRISPR technologies,particularly technological advances in CRISPR screens and their application in novel target identification for immunotherapy.
      原文链接:
    • 万方数据
    • 维普

    CRISPR beyond:harnessing compact RNA-guided endonucleases for enhanced genome editing

    Feizuo WangShengsheng MaSenfeng ZhangQuanquan Ji...
    2563-2574页
    查看更多>>摘要：The CRISPR-Cas system,an adaptive immunity system in prokaryotes designed to combat phages and foreign nucleic acids,has evolved into a groundbreaking technology enabling gene knockout,large-scale gene insertion,base editing,and nucleic acid detection.Despite its transformative impact,the conventional CRISPR-Cas effectors face a significant hurdle—their size poses challenges in effective delivery into organisms and cells.Recognizing this limitation,the imperative arises for the development of compact and miniature gene editors to propel advancements in gene-editing-related therapies.Two strategies were accepted to develop compact genome editors:harnessing OMEGA(Obligate Mobile Element-guided Activity)systems,or engineering the existing CRISPR-Cas system.In this review,we focus on the advances in miniature genome editors based on both of these strategies.The objective is to unveil unprecedented opportunities in genome editing by embracing smaller,yet highly efficient genome editors,promising a future characterized by enhanced precision and adaptability in the genetic interventions.
      原文链接:
    • 万方数据
    • 维普

    Lipid nanoparticle-mediated base-editing of the Hao1 gene achieves sustainable primary hyperoxaluria type 1 therapy in rats

    Dexin ZhangRui ZhengZhoutong ChenLiren Wang...
    2575-2586页
    查看更多>>摘要：Primary hyperoxaluria type 1(PH1)is a severe hereditary disease,leading to the accumulation of oxalate in multiple organs,particularly the kidney.Hydroxyacid oxidase 1(HAO1),a pivotal gene involved in oxalate production,is an approved target for the treatment of PH1.In this study,we demonstrated the discovery of several novel therapeutic sites of the Hao1 gene and the efficient editing of Hao1 c.290-2 A in vivo with lipid nanoparticles(LNP)delivered adenine base editing(ABE)mRNA.A single infusion of LNP-ABE resulted in a near-complete knockout of Hao1 in the liver,leading to the sustainable normalization of urinary oxalate(for at least 6 months)and complete rescue of the patho-physiology in PH1 rats.Additionally,a significant correlation between Hao1 editing efficiency and urinary oxalate levels was observed and over 60％Hao1 editing efficiency was required to achieve the normalization of urinary oxalate in PH1 rats.These findings suggest that the LNP-mediated base-editing of Hao1 c.290-2 A is an efficient and safe approach to PH1 therapy,highlighting its potential utility in clinical settings.
      原文链接:
    • 万方数据
    • 维普

    rAAV-CRISPR/Cas9-mediated in vivo delivery of porcine embryos to construct knockout pigs

    Mengyu GaoYuTing HeXingLong ZhuWanLiu Peng...
    2587-2589页
      原文链接:
    • 万方数据
    • 维普

    Gut microbiota and healthy longevity

    Jia LuoShan LiangFeng Jin
    2590-2602页
    查看更多>>摘要：Recent progress on the underlying biological mechanisms of healthy longevity has propelled the field from elucidating genetic modification of healthy longevity hallmarks to defining mechanisms of gut microbiota influencing it.Importantly,the role of gut microbiota in the healthy longevity of the host may provide unprecedented opportunities to decipher the plasticity of lifespan on a natural evolutionary scale and shed light on using microbiota-targeted strategies to promote healthy aging and combat age-related diseases.This review investigates how gut microbiota affects healthy longevity,focusing on the mechanisms through which gut microbiota modulates it.Specifically,we focused on the ability of gut microbiota to enhance the intestinal barrier integrity,provide protection from inflammaging,ameliorate nutrientsensing pathways,optimize mitochondrial function,and improve defense against age-related diseases,thus participating in en-hancing longevity and healthspan.
      原文链接:
    • 万方数据
    • 维普

    Unlocking the potential:advancements and future horizons in ROR1-targeted cancer therapies

    Lin LiWeixue HuangXiaomei RenZhen Wang...
    2603-2616页
    查看更多>>摘要：While receptor tyrosine kinase-like orphan receptor 1(ROR1)is typically expressed at low levels or absent in normal tissues,its expression is notably elevated in various malignant tumors and conditions,including chronic lymphocytic leukemia(CLL),breast cancer,ovarian cancer,melanoma,and lung adenocarcinoma.This distinctive feature positions ROR1 as an attractive target for tumor-specific treatments.Currently,several targeted drugs directed at ROR1 are undergoing clinical development,including monoclonal antibodies,antibody-drug conjugates(ADCs),and chimeric antigen receptor T-cell therapy(CAR-T).Additionally,there are four small molecule inhibitors designed to bind to ROR1,presenting promising avenues for the development of PROTAC degraders targeting ROR1.This review offers updated insights into ROR1's structural and functional characteristics,embryonic development implications,cell survival signaling pathways,and evolu-tionary targeting strategies,all of which have the potential to advance the treatment of malignant tumors.
      原文链接:
    • 万方数据
    • 维普

    Crop antiviral defense:Past and future perspective

    Zhirui YangGuangyao LiYongliang ZhangFangfang Li...
    2617-2634页
    查看更多>>摘要：Viral pathogens not only threaten the health and life of humans and animals but also cause enormous crop yield losses and contribute to global food insecurity.To defend against viral pathogens,plants have evolved an intricate immune system to perceive and cope with such attacks.Although most of the fundamental studies were carried out in model plants,more recent research in crops has provided new insights into the antiviral strategies employed by crop plants.We summarize recent advances in understanding the biological roles of cellular receptors,RNA silencing,RNA decay,hormone signaling,autophagy,and ubiquitination in manipulating crop host-mediated antiviral responses.The potential functions of circular RNAs,the rhizosphere microbiome,and the foliar microbiome of crops in plant-virus interactions will be fascinating research directions in the future.These findings will be beneficial for the development of modern crop improvement strategies.
      原文链接:
    • 万方数据
    • 维普

    Increase of PCSK9 expression in diabetes promotes VEGFR2 ubiquitination to inhibit endothelial function and skin wound healing

    Jian-Jun GaoFang-Yuan WuYu-Jia LiuLe Li...
    2635-2649页
    查看更多>>摘要：Diabetic foot ulcers(DFUs)are a serious vascular disease.Currently,no effective methods are available for treating DFUs.Pro-protein convertase subtilisin/kexin type 9(PCSK9)regulates lipid levels to promote atherosclerosis.However,the role of PCSK9 in DFUs remains unclear.In this study,we found that the expression of PCSK9 in endothelial cells(ECs)increased significantly under high glucose(HG)stimulation and in diabetic plasma and vessels.Specifically,PCSK9 promotes the E3 ubiquitin-protein ligase NEDD4 binding to vascular endothelial growth factor receptor 2(VEGFR2),which led to the ubiquitination of VEGFR2,resulting in its degradation and downregulation in ECs.Furthermore,PCSK9 suppresses the expression and activation of AKT,endothelial nitric oxide synthase(eNOS),and ERK1/2,leading to decreased nitric oxide(NO)production and increased superoxide anion(O2·-)generation,which impairs vascular endothelial function and angiogenesis.Importantly,using evolocumab to limit the increase in PCSK9 expression blocked the HG-induced inhibition of NO production and the increase in O2·- production,as well as inhibited the phosphorylation and expression of AKT,eNOS,and ERK1/2.Moreover,evolocumab improved vascular endothelial function and angiogenesis,and promoted wound healing in diabetes.Our findings suggest that targeting PCSK9 is a novel therapeutic approach for treating DFUs.
      原文链接:
    • 万方数据
    • 维普