本草小核酸(sRNA)数据库的综合分析——揭示人类疾病的新疗法  

A comprehensive analysis of the Bencao(herbal)small RNA Atlas reveals novel RNA therapeutics for treating human diseases

作　　者：曹英豪 林烨暄 孙娜 杜芯仪 董一昕 梅颂 邓兴宇 李晓北 郭劭婷 汤克功 刘佳齐 乔翔宇 赵丹丹 秦宇豪 张聪 辛天怡[2] 史晓虎 周丛照[4] 董涛 果德安 Benedikt M.Kessler 许东 宋经元[2] 黄凤鸣[1] 王晓月 蒋澄宇[1] CAO YingHao;LIN YeXuan;SUN Na;DU XinYi;DONG YiXin;MEI Song;DENG XingYu;LI XiaoBei;GUO ShaoTing;TANG KeGong;LIU JiaQi;QIAO XiangYu;ZHAO DanDan;QIN YuHao;ZHANG Cong;XIN TianYi;SHI XiaoHu;ZHOU CongZhao;DONG Tao;GUO De-An;Benedikt M.Kessler;XU Dong;SONG JingYuan;HUANG FengMing;WANG XiaoYue;JIANG ChengYu(State Key Laboratory of Common Mechanism Research for Major Diseases,Department of Biochemistry,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,School of Basic Medicine Peking Union Medical College,Beijing 100005,China;Key Laboratory of Chinese Medicine Resources Conservation,State Administration of Traditional Chinese Medicine of China,Engineering Research Center of Chinese Medicine Resource of Ministry of Education,Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100193,China;Department of Traditional Chinese Medicine,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100005,China;Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences,University of Science and Technology of China,Hefei 230027,China;MRC Human Immunology Unit,MRC Weatherall Institute of Molecular Medicine,Radcliffe Department of Medicine,University of Oxford,Oxford OX37FZ,UK;Chinese Academy of Medical Sciences(CAMS),CAMS Oxford Institute(COI),Nuffield Department of Medicine,University of Oxford,Oxford OX37FZ,UK;Shanghai Research Center for Modernization of Traditional Chinese Medicine,National Engineering Laboratory for TCM Standardization Technology,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;Target Discovery Institute,Centre for Medicines Discovery,Nuffield Department of Medicine,University of Oxford,Oxford OX37FZ,UK;Department of Electrical Engineering and Computer Science,and Christopher S.Bond Life Sciences Center,University of Missouri,Columbia MO 65211,USA)

机构地区：[1]中国医学科学院基础医学研究所&北京协和医学院基础学院,生物化学与分子生物学系,重大疾病共性机制研究全国重点实验室,北京100005 [2]中国医学科学院北京协和医学院药用植物研究所,国家中医药管理局中药资源保护重点研究室,中药资源教育部工程研究中心,北京100193 [3]中国医学科学院&北京协和医学院,北京协和医院中医科,北京100005 [4]中国科学技术大学生命科学学院,合肥微尺度物质科学国家研究中心,合肥230027 [5]MRC Human Immunology Unit,MRC Weatherall Institute of Molecular Medicine,Radcliffe Department of Medicine,University of Oxford,Oxford OX37FZ,UK [6]Chinese Academy of Medical Sciences(CAMS),CAMS Oxford Institute(COI),Nuffield Department of Medicine,University of Oxford,Oxford OX37FZ,UK [7]中国科学院上海药物研究所,上海中药现代化研究中心,中药标准化技术国家工程实验室,上海201203 [8]Target Discovery Institute,Centre for Medicines Discovery,Nuffield Department of Medicine,University of Oxford,Oxford OX37FZ,UK [9]Department of Electrical Engineering and Computer Science,and Christopher S.Bond Life Sciences Center,University of Missouri,Columbia MO 65211,USA

出　　处：《中国科学：生命科学》2024年第12期2438-2458,共21页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:81788101,32100104);中国医学科学院医学与健康科技创新工程重大协同创新项目(批准号:2021-I2M-1-022);中国医学科学院捐赠项目(批准号:2021-CAMS-JZ001);高等学校学科创新引智计划2.0(111计划2.0)(批准号:BP0820029)资助。

摘　　要：2012年首次报道了稻米来源的miRNA的跨界调控.通过改良的草药提取方法和高通量测序技术,本研究从245种中药(traditional Chinese medicine,TCM)中获得了73677287条小核酸(small RNA,sRNA)序列,其中包含20758257条去冗余后的独特序列.本研究构建了本草小核酸数据库(Bencao(herbal)small RNA Atlas)(http://bencao.bmicc.cn),同时基于序列分析,进行sRNAs注释并建立了本草小核酸命名系统.经计算分析,本草小核酸数据库中的21757条miRNAs与收录于miRBase数据库中的植物miRNAs的特征图谱高度一致.多种软件计算分析结果表明,人类所有编码基因都有可能受来自本草小核酸数据库中的sRNAs的调控,本研究通过实验验证了其中一部分的预测计算结果.这些结果显示,本草来源的sRNAs可能是中草药的新的重要药效活性成分.本研究提出了基于本草小核酸数据库的寡核苷酸药物的研发路径和中药处方的优化策略路线图.此外,中药汤剂体(decoctosome)是中药水煎液中的脂质纳米颗粒,其质量约占中药水煎液的0.5%~2.5%,却展示出显著的药效.本研究提出了新的可用于定量衡量草药药效标准的本草指数,包括小分子化合物(small-molecule compounds,SM)、蛋白多肽(protein peptides,P)、核酸(nucleic acid,N)、非核酸非蛋白大分子化合物(large-molecule compounds,LM)和门捷列夫周期表中的相关元素(E).本研究构建的本草小核酸数据库,可用于寡核苷酸药物的开发和植物药的优化,并为易(壹)医学理论提供了科学依据.Cross-kingdom herbal miRNA was first reported in 2012.Using a modified herbal extraction protocol,we obtained 73677287 sequences by RNA-seq from 245 traditional Chinese Medicine(TCM),of which 20758257 were unique sequences.We constructed a Bencao(herbal)small RNA(sRNA)Atlas(http://bencao.bmicc.cn),annotated the sequences by sequence-based clustering,and created a nomenclature system for Bencao sRNAs.The profiles of 21,757 miRNAs in the Atlas were highly consistent with those of plant miRNAs in miRBase.Using software tools,our results demonstrated that all human genes might be regulated by sRNAs from the Bencao sRNA Atlas,part of the predicted human target genes were experimentally validated,suggesting that Bencao sRNAs might be one of the main bioactive components of herbal medicines.We established roadmaps for oligonucleotide drugs development and optimization of TCM prescriptions.Moreover,the decoctosome,a lipo-nano particle consisting of 0.5%–2.5%of the decoction,demonstrated potent medical effects.We propose a Bencao(herbal)Index,including small-molecule compounds(SM),protein peptides(P),nucleic acid(N),non-nucleic and non-proteinogenic large-molecule compounds(LM)and elements from Mendeleev’s periodic table(E),to quantitatively measure the medical effects of botanic medicine.The Bencao sRNA Atlas is a resource for developing gene-targeting oligonucleotide drugs and optimizing botanical medicine,and may provide potential remedies for the theory and practice of one medicine.

关 键 词：小核酸 中药水煎液 跨界调控 中药 寡核苷酸药物 核酸治疗 本草小核酸数据库 

分 类 号：R281[医药卫生—中药学]