合成生物学 — 生命科学的下一个风口
<div style="max-width:100%;overflow:hidden;"><section style="font-size: 15px;color: rgb(24, 24, 27);line-height: 2;box-sizing: border-box;font-style: normal;font-weight: 400;text-align: justify;" data-mpa-powered-by="yiban.io"><section style="text-align: center;margin: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br></section><section style="text-align: center;justify-content: center;margin: 0px 0%;display: flex;flex-flow: row nowrap;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 100%;vertical-align: top;background-color: rgb(237, 247, 245);padding: 5px;border-style: solid;border-width: 0px;border-color: rgb(62, 62, 62);flex: 0 0 auto;height: auto;overflow: hidden;align-self: flex-start;box-sizing: border-box;"><section style="justify-content: center;display: flex;flex-flow: row nowrap;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 100%;vertical-align: top;border-width: 3px;border-style: solid;border-color: rgb(255, 255, 255);padding: 15px;align-self: flex-start;flex: 0 0 auto;box-sizing: border-box;"><section style="text-align: justify;box-sizing: border-box;" powered-by="xiumi.us"><p style="text-indent: 2em;white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;">如果要论2022年生命科学最火赛道，那非<span style="color: rgb(0, 136, 111);box-sizing: border-box;"><strong style="box-sizing: border-box;">合成生物学</strong></span>莫属。2021年至今，全球资本市场上刮起一阵合成生物学风。据SynBioBeta统计，2021年全球合成生物学投融资金额达到180亿美元。国内合成生物学赛道同样炙手可热，多家头部投资机构纷纷布局，新兴交叉学科“合成生物学”在学界、业界备受瞩目。</p></section><section style="text-align: right;margin: 15px 0px 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 60px;height: 60px;vertical-align: top;overflow: hidden;border-width: 2px;border-radius: 100%;border-style: dotted;border-color: rgb(0, 136, 111);padding: 5px;box-sizing: border-box;"><section style="text-align: center;margin: 0px 0%;box-sizing: border-box;" powered-by="xiumi.us"><section style="max-width: 100%;vertical-align: middle;display: inline-block;line-height: 0;width: 100%;height: auto;box-sizing: border-box;"></section></section></section></section></section></section></section></section><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="text-align: center;margin: 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="max-width: 100%;vertical-align: middle;display: inline-block;line-height: 0;box-sizing: border-box;"></section></section><section style="margin: 10px 0px 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: center;font-size: 12px;color: rgb(139, 139, 141);line-height: 1.6;box-sizing: border-box;"><p style="margin: 0px;padding: 0px;box-sizing: border-box;">图：全球合成生物学投融资趋势</p></section></section><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="display: flex;width: 100%;flex-flow: column nowrap;box-sizing: border-box;" powered-by="xiumi.us"><section style="height: auto;z-index: 1;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: flex;flex-flow: row nowrap;margin: 10px 0% -18px;text-align: center;justify-content: center;box-sizing: border-box;"><section style="display: inline-block;vertical-align: top;width: 28px;flex: 0 0 auto;height: auto;align-self: flex-start;margin: 0px -13px 0px 0px;box-sizing: border-box;"><section style="transform: rotateZ(322deg);box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: right;margin: 7px 0% 0px;box-sizing: border-box;"><section style="display: inline-block;width: 10px;height: 18px;vertical-align: top;overflow: hidden;border-width: 0px;border-radius: 17px;border-style: none;border-color: rgb(62, 62, 62);background-color: rgba(255, 255, 255, 0);box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section></section><section style="display: inline-block;vertical-align: top;width: auto;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;align-self: flex-start;box-sizing: border-box;"><section style="margin: 0px 0%;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 38px;height: 38px;vertical-align: top;overflow: hidden;border-width: 0px;border-radius: 245px;border-style: none;border-color: rgb(62, 62, 62);background-color: rgb(0, 136, 111);box-sizing: border-box;"><section style="margin: 6px 0% 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="color: rgb(255, 255, 255);font-size: 16px;line-height: 1.6;box-sizing: border-box;"><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">1</strong></p></section></section></section></section></section></section></section></section><section style="margin: 0px 0% 10px;text-align: center;justify-content: center;display: flex;flex-flow: row nowrap;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 100%;vertical-align: top;background-color: rgb(237, 247, 245);flex: 0 0 auto;height: auto;margin: 0px;padding: 20px 20px 10px;align-self: flex-start;box-sizing: border-box;"><section style="margin: 0px 0%;box-sizing: border-box;" powered-by="xiumi.us"><section style="font-size: 17px;color: rgb(0, 136, 111);box-sizing: border-box;"><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">开启“造物”时代，合成生物学起源</strong></p></section></section></section></section><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><p style="text-indent: 2em;white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us">1978年，出生在波兰的遗传学家瓦克劳·希巴尔斯基( Waclaw Szybalski )在自己发表的学术期刊论文中，第一次使用了“合成生物学”（Synthetic Biology）这一词汇。而到了21世纪，斯坦福大学教授库尔（ EricT.Kool ）在2000年美国化学年会上重新定义合成生物学概念，让合成生物学成为一门新学科。2004年，合成生物学被评为《麻省理工科技评论》评为改变世界的十大新技术之一。2013年，CRISPR-Cas9基因编辑技术横空出世，给生物技术产业带来巨大变革，并于2020年获得诺贝尔化学奖。合成生物学的大幕由此拉开，成为国际科学前沿的热门方向。</p><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="display: flex;width: 100%;flex-flow: column nowrap;box-sizing: border-box;" powered-by="xiumi.us"><section style="height: auto;z-index: 1;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: flex;flex-flow: row nowrap;margin: 10px 0% -18px;text-align: center;justify-content: center;box-sizing: border-box;"><section style="display: inline-block;vertical-align: top;width: 28px;flex: 0 0 auto;height: auto;align-self: flex-start;margin: 0px -13px 0px 0px;box-sizing: border-box;"><section style="transform: rotateZ(322deg);box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: right;margin: 7px 0% 0px;box-sizing: border-box;"><section style="display: inline-block;width: 10px;height: 18px;vertical-align: top;overflow: hidden;border-width: 0px;border-radius: 17px;border-style: none;border-color: rgb(62, 62, 62);background-color: rgba(255, 255, 255, 0);box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section></section><section style="display: inline-block;vertical-align: top;width: auto;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;align-self: flex-start;box-sizing: border-box;"><section style="margin: 0px 0%;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 38px;height: 38px;vertical-align: top;overflow: hidden;border-width: 0px;border-radius: 245px;border-style: none;border-color: rgb(62, 62, 62);background-color: rgb(0, 136, 111);box-sizing: border-box;"><section style="margin: 6px 0% 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="color: rgb(255, 255, 255);font-size: 16px;line-height: 1.6;box-sizing: border-box;"><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">2</strong></p></section></section></section></section></section></section></section></section><section style="margin: 0px 0% 10px;text-align: center;justify-content: center;display: flex;flex-flow: row nowrap;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 100%;vertical-align: top;background-color: rgb(237, 247, 245);flex: 0 0 auto;height: auto;margin: 0px;padding: 20px 20px 10px;align-self: flex-start;box-sizing: border-box;"><section style="margin: 0px 0%;box-sizing: border-box;" powered-by="xiumi.us"><section style="font-size: 17px;color: rgb(0, 136, 111);box-sizing: border-box;"><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">合成生物学开启生命科学革命大门</strong></p></section></section></section></section><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><p style="text-indent: 2em;white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><span style="color: rgb(0, 136, 111);box-sizing: border-box;"><strong style="box-sizing: border-box;">合成生物学是生物学、生物信息学、计算机科学、化学、材料学等多学科交叉融合的结晶</strong></span>，实现的技术路径是运用系统生物学和工程学原理，以基因组和生化分子合成为基础，综合生物化学、生物物理和生物信息等技术，旨在设计、改造、重建生物分子、生物元件和生物分化过程，以构建具有生命活性的生物元件、系统以及人造细胞或生物体。</p><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="text-align: center;margin: 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="max-width: 100%;vertical-align: middle;display: inline-block;line-height: 0;box-sizing: border-box;"></section></section><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us">合成生物学的发展变革经历以下时期：</p><section style="display: flex;flex-flow: row nowrap;text-align: left;justify-content: flex-start;margin: 15px 0px 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;vertical-align: top;width: auto;align-self: flex-start;flex: 0 0 0%;height: auto;box-sizing: border-box;"><section style="text-align: center;transform: translate3d(4px, 0px, 0px);margin: 10px 0% 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 7px;height: 7px;vertical-align: top;overflow: hidden;border-width: 0px;border-radius: 2px;border-style: none;border-color: rgb(62, 62, 62);background-color: rgb(0, 136, 111);box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section><section style="display: inline-block;vertical-align: top;width: auto;border-left: 1px solid rgb(0, 136, 111);border-bottom-left-radius: 0px;flex: 100 100 0%;align-self: flex-start;height: auto;padding: 0px 0px 16px 16px;box-sizing: border-box;"><section style="color: rgb(24, 24, 27);padding: 0px;text-align: justify;box-sizing: border-box;" powered-by="xiumi.us"><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;"><span style="color: rgb(0, 136, 111);box-sizing: border-box;"><strong style="box-sizing: border-box;">萌芽期(2005年以前)：</strong></span>基因线路在代谢工程领域的应用是这一时期的代表。典型成果:青蒿素前体在大肠杆菌中的合成。</p></section></section></section><section style="display: flex;flex-flow: row nowrap;text-align: left;justify-content: flex-start;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;vertical-align: top;width: auto;align-self: flex-start;flex: 0 0 0%;height: auto;box-sizing: border-box;"><section style="text-align: center;transform: translate3d(4px, 0px, 0px);margin: 10px 0% 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 7px;height: 7px;vertical-align: top;overflow: hidden;border-width: 0px;border-radius: 2px;border-style: none;border-color: rgb(62, 62, 62);background-color: rgb(0, 136, 111);box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section><section style="display: inline-block;vertical-align: top;width: auto;border-left: 1px solid rgb(0, 136, 111);border-bottom-left-radius: 0px;flex: 100 100 0%;align-self: flex-start;height: auto;padding: 0px 0px 16px 16px;box-sizing: border-box;"><section style="color: rgb(24, 24, 27);padding: 0px;text-align: justify;box-sizing: border-box;" powered-by="xiumi.us"><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;"><span style="color: rgb(0, 136, 111);box-sizing: border-box;"><strong style="box-sizing: border-box;">起步期(2005-2011年)：</strong></span>基础研究快速发展，工程化理念日渐深入，使能技术平台得到重视，方法以及工具不断开发，“工程生物学”早期发展。</p></section></section></section><section style="display: flex;flex-flow: row nowrap;text-align: left;justify-content: flex-start;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;vertical-align: top;width: auto;align-self: flex-start;flex: 0 0 0%;height: auto;box-sizing: border-box;"><section style="text-align: center;transform: translate3d(4px, 0px, 0px);margin: 10px 0% 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 7px;height: 7px;vertical-align: top;overflow: hidden;border-width: 0px;border-radius: 2px;border-style: none;border-color: rgb(62, 62, 62);background-color: rgb(0, 136, 111);box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section><section style="display: inline-block;vertical-align: top;width: auto;border-left: 1px solid rgb(0, 136, 111);border-bottom-left-radius: 0px;flex: 100 100 0%;align-self: flex-start;height: auto;padding: 0px 0px 16px 16px;box-sizing: border-box;"><section style="color: rgb(24, 24, 27);padding: 0px;text-align: justify;box-sizing: border-box;" powered-by="xiumi.us"><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;"><span style="color: rgb(0, 136, 111);box-sizing: border-box;"><strong style="box-sizing: border-box;">成长期(2011-2015年)：</strong></span>基因组编辑效率大幅提升，技术开发和应用不断拓展，技术的应用从生物基化学品、生物能源拓展至疾病诊断、药物和疫苗开发、作物育种、环境监测、生物新材料等诸多领域。</p></section></section></section><section style="display: flex;flex-flow: row nowrap;text-align: left;justify-content: flex-start;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;vertical-align: top;width: auto;align-self: flex-start;flex: 0 0 0%;height: auto;box-sizing: border-box;"><section style="text-align: center;transform: translate3d(4px, 0px, 0px);margin: 10px 0% 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 7px;height: 7px;vertical-align: top;overflow: hidden;border-width: 0px;border-radius: 2px;border-style: none;border-color: rgb(62, 62, 62);background-color: rgb(0, 136, 111);box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section><section style="display: inline-block;vertical-align: top;width: auto;border-left: 1px solid rgb(0, 136, 111);border-bottom-left-radius: 0px;flex: 100 100 0%;align-self: flex-start;height: auto;padding: 0px 0px 16px 16px;box-sizing: border-box;"><section style="color: rgb(24, 24, 27);padding: 0px;text-align: justify;box-sizing: border-box;" powered-by="xiumi.us"><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;"><span style="color: rgb(0, 136, 111);box-sizing: border-box;"><strong style="box-sizing: border-box;">创新阶段(2015年以后)：</strong></span>合成生物学“设计一构建一测试”(Design-Build-Test，DBT)循环拓展至“设计-构建-测试-学习”(Design-Build-Test-Learn，DBTL)。生物技术与信息技术融合发展特点更加明显，半导体合成生物学、工程生物学等理念相继提出。</p></section></section></section><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="display: flex;width: 100%;flex-flow: column nowrap;box-sizing: border-box;" powered-by="xiumi.us"><section style="height: auto;z-index: 1;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: flex;flex-flow: row nowrap;margin: 10px 0% -18px;text-align: center;justify-content: center;box-sizing: border-box;"><section style="display: inline-block;vertical-align: top;width: 28px;flex: 0 0 auto;height: auto;align-self: flex-start;margin: 0px -13px 0px 0px;box-sizing: border-box;"><section style="transform: rotateZ(322deg);box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: right;margin: 7px 0% 0px;box-sizing: border-box;"><section style="display: inline-block;width: 10px;height: 18px;vertical-align: top;overflow: hidden;border-width: 0px;border-radius: 17px;border-style: none;border-color: rgb(62, 62, 62);background-color: rgba(255, 255, 255, 0);box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section></section><section style="display: inline-block;vertical-align: top;width: auto;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;align-self: flex-start;box-sizing: border-box;"><section style="margin: 0px 0%;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 38px;height: 38px;vertical-align: top;overflow: hidden;border-width: 0px;border-radius: 245px;border-style: none;border-color: rgb(62, 62, 62);background-color: rgb(0, 136, 111);box-sizing: border-box;"><section style="margin: 6px 0% 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="color: rgb(255, 255, 255);text-align: justify;font-size: 16px;line-height: 1.6;box-sizing: border-box;"><p style="text-align: center;white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">3</strong></p></section></section></section></section></section></section></section></section><section style="margin: 0px 0% 10px;text-align: center;justify-content: center;display: flex;flex-flow: row nowrap;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 100%;vertical-align: top;background-color: rgb(237, 247, 245);flex: 0 0 auto;height: auto;margin: 0px;padding: 20px 20px 10px;align-self: flex-start;box-sizing: border-box;"><section style="margin: 0px 0%;box-sizing: border-box;" powered-by="xiumi.us"><section style="font-size: 17px;color: rgb(0, 136, 111);box-sizing: border-box;"><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;"><span style="box-sizing: border-box;">合成生物学的红利：</span></strong></p><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">市场潜力巨大和应用领域广泛</strong></p></section></section></section></section><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><p style="text-indent: 2em;white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us">根据麦肯锡2021年合成生物学报告数据显示，全球60%的产品都可以利用生物技术生产，其中1/3来自自然界提取的物质和2/3非自然界直接来源，合成生物学改变他们生产方式，预计未来10-20年，合成生物学将拥有2000-3000亿美元的空间。<span style="color: rgb(0, 136, 111);box-sizing: border-box;"><strong style="box-sizing: border-box;">根据Markets and Markets的报告，全球合成生物学市场预计将从2021年的95亿美元增长到2026年的307亿美元，年复合增长率为26.5%。</strong></span></p><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="text-align: center;margin: 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="max-width: 100%;vertical-align: middle;display: inline-block;line-height: 0;box-sizing: border-box;"></section></section><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><p style="text-indent: 2em;white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><span style="color: rgb(0, 136, 111);box-sizing: border-box;"><strong style="box-sizing: border-box;">从全球范围内不同领域市场规模来看，与医疗健康相关的应用主导了合成生物学行业的商业化</strong></span>，而在食品、农业、消费品以及化工领域，孕育着重要的市场机遇，相关细分市场空间正在以高 CAGR 的水平增长。</p><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="text-align: center;margin: 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="max-width: 100%;vertical-align: middle;display: inline-block;line-height: 0;box-sizing: border-box;"></section></section><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="display: flex;width: 100%;flex-flow: column nowrap;box-sizing: border-box;" powered-by="xiumi.us"><section style="height: auto;z-index: 1;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: flex;flex-flow: row nowrap;margin: 10px 0% -18px;text-align: center;justify-content: center;box-sizing: border-box;"><section style="display: inline-block;vertical-align: top;width: 28px;flex: 0 0 auto;height: auto;align-self: flex-start;margin: 0px -13px 0px 0px;box-sizing: border-box;"><section style="transform: rotateZ(322deg);box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: right;margin: 7px 0% 0px;box-sizing: border-box;"><section style="display: inline-block;width: 10px;height: 18px;vertical-align: top;overflow: hidden;border-width: 0px;border-radius: 17px;border-style: none;border-color: rgb(62, 62, 62);background-color: rgba(255, 255, 255, 0);box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section></section><section style="display: inline-block;vertical-align: top;width: auto;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;align-self: flex-start;box-sizing: border-box;"><section style="margin: 0px 0%;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 38px;height: 38px;vertical-align: top;overflow: hidden;border-width: 0px;border-radius: 245px;border-style: none;border-color: rgb(62, 62, 62);background-color: rgb(0, 136, 111);box-sizing: border-box;"><section style="margin: 6px 0% 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="color: rgb(255, 255, 255);font-size: 16px;line-height: 1.6;box-sizing: border-box;"><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">4</strong></p></section></section></section></section></section></section></section></section><section style="margin: 0px 0% 10px;text-align: center;justify-content: center;display: flex;flex-flow: row nowrap;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: 100%;vertical-align: top;background-color: rgb(237, 247, 245);flex: 0 0 auto;height: auto;margin: 0px;padding: 20px 20px 10px;align-self: flex-start;box-sizing: border-box;"><section style="margin: 0px 0%;box-sizing: border-box;" powered-by="xiumi.us"><section style="font-size: 17px;color: rgb(0, 136, 111);box-sizing: border-box;"><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">颠覆性的技术支撑合成生物学发展， </strong></p><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">“上帝之手”让万物皆可合成</strong></p></section></section></section></section><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="box-sizing: border-box;" powered-by="xiumi.us"><p style="margin: 0px 0px 15px;text-indent: 2em;white-space: normal;padding: 0px;box-sizing: border-box;"><span style="color: rgb(0, 136, 111);box-sizing: border-box;"><strong style="box-sizing: border-box;">2013年，被誉为“上帝之手”的CRISPR-Cas9基因编辑技术横空出世，从此人类可以修改DNA序列</strong></span>，这项技术也在2020年荣获诺贝尔化学奖。CRISPR技术在合成生物学标准化模块化发展过程中发挥着重要作用。颠覆性的技术是支撑合成生物学发展的关键，基因合成、基因编辑、蛋白质设计、细胞设计、高通量筛选等技术的发展对合成生物学的发展有着重要的支撑和推动作用，而DNA/RNA 的编辑、合成和组装技术是合成生物学产业的基础。根据BCC Research统计，DNA合成以及编辑应用市场从2019年的170美元增长到2024年431亿美元。</p><p style="margin: 0px 0px 15px;text-indent: 2em;white-space: normal;padding: 0px;box-sizing: border-box;"><span style="color: rgb(0, 136, 111);box-sizing: border-box;"><strong style="box-sizing: border-box;">目前DNA合成技术中主要分为化学合成法以及酶促合成法</strong></span>，DNA化学合成法是当前主流的商业化合成方法。从柱式合成演变到芯片合成，一般分为四个步骤：Design–Build–Test–Learn，首先筛选设计底盘菌，再使用计算机设计DNA，然后培养测试底盘细胞等，在生物制造厂经历一整套工业化流程。</p><p style="text-indent: 2em;white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;">DNA/RNA 的合成有磷酸三酯法、亚磷酰胺法、氢磷酸法等，现在常用的是固相亚磷酰胺法。它具有快速、方便、偶联效率高等特点。一般从 3′向 5′合成，通过下列四个步骤加上一个核苷酸。</p></section><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="text-align: center;margin: 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="max-width: 100%;vertical-align: middle;display: inline-block;line-height: 0;box-sizing: border-box;"></section></section><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="text-align: left;justify-content: flex-start;display: flex;flex-flow: row nowrap;margin: 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;vertical-align: middle;width: auto;line-height: 0;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;align-self: center;box-sizing: border-box;"><section style="transform: rotateZ(45deg);box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: center;margin: 0px 0%;box-sizing: border-box;"><section style="display: inline-block;width: 15px;height: 4px;vertical-align: top;overflow: hidden;background-color: rgb(0, 136, 111);border-width: 0px;border-radius: 10px;border-style: none;border-color: rgb(62, 62, 62);box-shadow: rgb(0, 0, 0) 0px 0px 0px;box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section><section style="transform: rotateZ(315deg);box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: center;margin: 4px 0% 5px;box-sizing: border-box;"><section style="display: inline-block;width: 14px;height: 4px;vertical-align: top;overflow: hidden;background-color: rgb(153, 207, 197);border-width: 0px;border-radius: 10px;border-style: none;border-color: rgb(62, 62, 62);box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section></section><section style="display: inline-block;vertical-align: middle;width: auto;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;align-self: center;box-sizing: border-box;"><section style="margin: 0px 0% 5px;box-sizing: border-box;" powered-by="xiumi.us"><section style="padding: 0px;text-align: center;color: rgb(0, 136, 111);line-height: 2;box-sizing: border-box;"><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">第一步：脱保护</strong></p></section></section></section></section><p style="text-indent: 2em;white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><span style="text-indent: 2em;box-sizing: border-box;">用三氯乙酸或二氯乙酸脱去连在固相载体上的核苷酸 5′羟基上的保护基团 DMT 使它暴露出来进行下一步反应。</span></p><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="text-align: left;justify-content: flex-start;display: flex;flex-flow: row nowrap;margin: 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;vertical-align: middle;width: auto;line-height: 0;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;align-self: center;box-sizing: border-box;"><section style="transform: rotateZ(45deg);box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: center;margin: 0px 0%;box-sizing: border-box;"><section style="display: inline-block;width: 15px;height: 4px;vertical-align: top;overflow: hidden;background-color: rgb(0, 136, 111);border-width: 0px;border-radius: 10px;border-style: none;border-color: rgb(62, 62, 62);box-shadow: rgb(0, 0, 0) 0px 0px 0px;box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section><section style="transform: rotateZ(315deg);box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: center;margin: 4px 0% 5px;box-sizing: border-box;"><section style="display: inline-block;width: 14px;height: 4px;vertical-align: top;overflow: hidden;background-color: rgb(153, 207, 197);border-width: 0px;border-radius: 10px;border-style: none;border-color: rgb(62, 62, 62);box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section></section><section style="display: inline-block;vertical-align: middle;width: auto;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;align-self: center;box-sizing: border-box;"><section style="margin: 0px 0% 5px;box-sizing: border-box;" powered-by="xiumi.us"><section style="padding: 0px;text-align: center;color: rgb(0, 136, 111);line-height: 2;box-sizing: border-box;"><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">第二步：偶联</strong></p></section></section></section></section><p style="text-indent: 2em;white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us">将亚磷酰胺单体用四唑活化，形成高反应性的亚磷酰四唑，进入合成柱，与连在固相载体上的寡核苷酸 5′羟基偶联这一步效率一般在 98% 以上。</p><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="text-align: left;justify-content: flex-start;display: flex;flex-flow: row nowrap;margin: 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;vertical-align: middle;width: auto;line-height: 0;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;align-self: center;box-sizing: border-box;"><section style="transform: rotateZ(45deg);box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: center;margin: 0px 0%;box-sizing: border-box;"><section style="display: inline-block;width: 15px;height: 4px;vertical-align: top;overflow: hidden;background-color: rgb(0, 136, 111);border-width: 0px;border-radius: 10px;border-style: none;border-color: rgb(62, 62, 62);box-shadow: rgb(0, 0, 0) 0px 0px 0px;box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section><section style="transform: rotateZ(315deg);box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: center;margin: 4px 0% 5px;box-sizing: border-box;"><section style="display: inline-block;width: 14px;height: 4px;vertical-align: top;overflow: hidden;background-color: rgb(153, 207, 197);border-width: 0px;border-radius: 10px;border-style: none;border-color: rgb(62, 62, 62);box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section></section><section style="display: inline-block;vertical-align: middle;width: auto;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;align-self: center;box-sizing: border-box;"><section style="margin: 0px 0% 5px;box-sizing: border-box;" powered-by="xiumi.us"><section style="padding: 0px;text-align: center;color: rgb(0, 136, 111);line-height: 2;box-sizing: border-box;"><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">第三步：氧化</strong></p></section></section></section></section><p style="text-indent: 2em;white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us">缩合反应时核苷酸单体是通过亚磷酯键与连在固相载体上的寡核苷酸连接，而亚磷酯键不稳定，易被酸、碱水解，此时常用碘的四氢呋喃溶液将亚磷酯转化为磷酸三酯，得到稳定的寡核苷酸。 </p><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><section style="text-align: left;justify-content: flex-start;display: flex;flex-flow: row nowrap;margin: 0px;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;vertical-align: middle;width: auto;line-height: 0;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;align-self: center;box-sizing: border-box;"><section style="transform: rotateZ(45deg);box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: center;margin: 0px 0%;box-sizing: border-box;"><section style="display: inline-block;width: 15px;height: 4px;vertical-align: top;overflow: hidden;background-color: rgb(0, 136, 111);border-width: 0px;border-radius: 10px;border-style: none;border-color: rgb(62, 62, 62);box-shadow: rgb(0, 0, 0) 0px 0px 0px;box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section><section style="transform: rotateZ(315deg);box-sizing: border-box;" powered-by="xiumi.us"><section style="text-align: center;margin: 4px 0% 5px;box-sizing: border-box;"><section style="display: inline-block;width: 14px;height: 4px;vertical-align: top;overflow: hidden;background-color: rgb(153, 207, 197);border-width: 0px;border-radius: 10px;border-style: none;border-color: rgb(62, 62, 62);box-sizing: border-box;"><svg viewBox="0 0 1 1" style="float:left;line-height:0;width:0;vertical-align:top;"></svg></section></section></section></section><section style="display: inline-block;vertical-align: middle;width: auto;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;align-self: center;box-sizing: border-box;"><section style="margin: 0px 0% 5px;box-sizing: border-box;" powered-by="xiumi.us"><section style="padding: 0px;text-align: center;color: rgb(0, 136, 111);line-height: 2;box-sizing: border-box;"><p style="margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">第四步：封闭</strong></p></section></section></section></section><p style="text-indent: 2em;white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us">为了防止少量未反应（2%）的连在固相载体上的 5′羟基进入下一循环，用醋酐对其进行乙酰化封闭，大大提高了最后产品的纯度。</p><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br style="box-sizing: border-box;"></p><p style="text-indent: 2em;white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us">经过上面四个步骤，核苷酸被逐个加到合成的寡核苷酸链上。最后用浓氨水把寡核苷酸从固相载体上切割下来，脱去碱基和磷酸基团上的保护基团，随后进行纯化和定量。</p><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;" powered-by="xiumi.us"><br></p><section style="margin: 0px 0% 5px;justify-content: flex-start;display: flex;flex-flow: row nowrap;box-sizing: border-box;" powered-by="xiumi.us"><section style="display: inline-block;width: auto;vertical-align: top;min-width: 10%;max-width: 100%;flex: 0 0 auto;height: auto;padding: 0px;border-bottom: 4px solid rgba(0, 136, 111, 0.35);border-bottom-right-radius: 0px;align-self: flex-start;box-sizing: border-box;"><section style="line-height: 1.5;box-sizing: border-box;" powered-by="xiumi.us"><p style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;"><strong style="box-sizing: border-box;">参考资料：</strong></p></section></section></section><section style="font-size: 12px;color: rgb(139, 139, 141);line-height: 1.6;text-align: left;box-sizing: border-box;" powered-by="xiumi.us"><p style="margin: 0px;padding: 0px;box-sizing: border-box;">1.天风证券-合成生物学-未来已来，开启造物时代</p><p style="margin: 0px;padding: 0px;box-sizing: border-box;">2.张媛媛,曾艳, 王钦宏. 合成生物制造进展.合成生物学, 2021, 2（2）:145-160.</p><p style="margin: 0px;padding: 0px;box-sizing: border-box;">3.BCG：synthetic biology is about to disrupt your industry</p></section></section>
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