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核酸疫苗研发态势与发展建议

李爱花,杨雪梅,孙轶楠,苑亚坤,杨俊涛

《中国工程科学》 2021年第23卷第4期页码 153-161 doi: 10.15302/J-SSCAE-2021.04.018

摘要：

应对新型冠状病毒肺炎（COVID-19）疫情防控的迫切需求，核酸疫苗以其快速高效的优点得到了疫苗研发领域的高度重视，特别是信使核糖核酸（mRNA）疫苗的研发进程显著加快，首次获批上市并在人体中使用。本文从核酸疫苗及相关技术概念、研发轨迹与发展趋势等方面总结梳理核酸疫苗的研发态势，辨识核酸疫苗特征，分析 COVID-19 疫情对 mRNA疫苗研究的促进作用，梳理核酸疫苗拓展应用的主要领域，针对可能存在的技术性研究建议，从改良目的基因表达、完善递送系统、提高免疫应答、增强 mRNA 稳定性及易存性等方面着手，着力开展核酸疫苗的关键技术开发；严格监管核酸疫苗的安全性和有效性；引导利益相关方对具有安全性风险、可能对肿瘤与传染病防控带来颠覆性影响的mRNA 疫苗技术开展改进研究，注重技术研发的前瞻布局并促进应用转化。

关键词：核酸疫苗脱氧核糖核酸（DNA）疫苗核糖核酸（RNA）疫苗信使核糖核酸（mRNA）疫苗新型冠状病毒肺炎肿瘤

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信息科学应引领未来的生物医学研究 Perspective

Kenta Nakai

《工程（英文）》 2019年第5卷第6期页码 1155-1158 doi: 10.1016/j.eng.2019.07.023

摘要：由于所有生命系统基本上都受其自身DNA中信息的支配，因此信息科学对生物医学的研究具有特别重要的意义。与物理学不同，在生物学中没有发现（或很少有）主导定律。NGS不仅用于“读取”DNA序列，而且还用于在单细胞水平上获得各种类型的信息。这些数据可以视为气候模拟中的网格数据点。

关键词：数据科学人工智能下一代测序脱氧核糖核酸癌症基因组单细胞转录组学

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疫苗获取难题促使发展中国家研发本土疫苗

Chris Palmer

《工程（英文）》 2022年第15卷第8期页码 3-5 doi: 10.1016/j.eng.2022.06.001

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药品监管科学推动中国新冠病毒疫苗研发概述 Review

黄志明, 付志浩, 王军志

《工程（英文）》 2022年第10卷第3期页码 127-132 doi: 10.1016/j.eng.2022.01.001

摘要：在甲型H1N1流感、严重急性呼吸综合征（SARS）和中东呼吸综合征（MERS）等传染病大流行期间，监管科学研究有力支持了抗病毒药物和疫苗的研发。特别在新型冠状病毒（简称新冠病毒）肺炎（COVID-19）疫情大流行期间，药品监管科学支持下的疫苗研发在疫情防控中发挥了重要作用。本文总结了中国疫苗产业、新冠病毒疫苗研发以及疫苗监管科学发展的总体概况。此外，本文重点从国家规划、法律法规、技术指南、质量控制和疫苗上市后监管等方面，回顾和分析了监管科学研究为推动中国新冠病毒疫苗研发所发挥的重要作用。本文为当前大流行阶段以及后疫情时代的疫苗研发策略制定提供参考，并为将来如何更好地应对新发和再发传染病提供借鉴和指导。

关键词：监管科学新冠病毒疫苗疫苗产业

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工程化DNA材料构建DNA活字系统实现可持续的数据存储 Article

巩子祎, 宋理富, 裴广胜, 董雨菲, 李炳志, 元英进

《工程（英文）》 2023年第29卷第10期页码 130-136 doi: 10.1016/j.eng.2022.05.023

摘要：

DNA分子作为一种具有潜力的数据存储绿色材料，具有密度高和保存期长的优势。然而，目前DNA数据存储的数据写入依赖于DNA从头合成，写入成本高昂，且产生有害物，限制了其实际应用。在本研究中，我们开发了一种DNA活字存储系统，该系统可以利用由细胞工厂预生产的DNA活字片段进行数据写入。在这个系统中，这些预先生成的DNA片段，在这里称为“DNA活字”，是可重复使用的基本数据单元。通过这些DNA活字的快速组装来实现数据写入，从而避免了昂贵且对环境有害的DNA化学合成过程。通过DNA活字片段的反复使用和生物组装，该系统在降低写入成本方面的潜力非常突出，为经济和可持续的DNA数据存储技术开辟了一条新颖路线。

关键词：合成生物学 DNA信息存储 DNA活字存储系统经济性DNA数据存储

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The role of PARP1 in the DNA damage response and its application in tumor therapy

null

《医学前沿（英文）》 2012年第6卷第2期页码 156-164 doi: 10.1007/s11684-012-0197-3

摘要：

Single-strand break repair protein poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the poly(ADP-ribosyl)ation of many key proteins in vivo and thus plays important roles in multiple DNA damage response pathways, rendering it a promising target in cancer therapy. The tumor-suppressor effects of PARP inhibitors have attracted significant interest for development of novel cancer therapies. However, recent evidence indicated that the underlying mechanism of PARP inhibitors in tumor therapy is more complex than previously expected. The present review will focus on recent progress on the role of PARP1 in the DNA damage response and PARP inhibitors in cancer therapy. The emerging resistance of BRCA-deficient tumors to PARP inhibitors is also briefly discussed from the perspective of DNA damage and repair. These recent research advances will inform the selection of patient populations who can benefit from the PARP inhibitor treatment and development of effective drug combination strategies.

关键词： PARP1 synthetic lethality PARP inhibitor DNA repair cancer NHEJ

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Functional role of ATM in the cellular response to DNA damage

Ming LIU, Wenxiang HU

《化学科学与工程前沿（英文）》 2011年第5卷第2期页码 179-187 doi: 10.1007/s11705-009-0268-4

摘要： Ataxia-telangiectasia mutated (ATM) plays a key role in regulating the cellular response to ionizing radiation. The tumor-suppressor gene ATM, mutations in which cause the human genetic disease ataxia telangiectasia, encodes a key protein kinase that controls the cellular response to double-stranded breaks. Activation of ATM results in phosphorylation of many downstream targets that modulate numerous damage response pathways, most notably cell cycle checkpoints. Here, we highlight some of the new developments in the field in our understanding of the mechanism of activation of ATM and its signaling pathways, explore whether DNA double-strand breaks are the sole activators of ATM and ATM-dependent signaling pathways, and address some of the prominent, unanswered questions related to ATM and its function. The scope of this article is to provide a brief overview of the recent literature on this subject and to raise questions that could be addressed in future studies.

关键词： ataxia-telangiectasia mutated (ATM) cell cycle checkpoint DNA damage signalling transduction

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李爱花：基于数据视角的核酸疫苗研发态势与发展建议（2021年9月3日）

2021年10月15日

关键词：医学

Generation and repair of AID-initiated DNA lesions in B lymphocytes

null

《医学前沿（英文）》 2014年第8卷第2期页码 201-216 doi: 10.1007/s11684-014-0324-4

摘要：

Activation-induced deaminase (AID) initiates the secondary antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation (SHM) and class switch recombination (CSR), both of which require AID. AID induces U:G mismatch lesions in DNA that are subsequently converted into point mutations or DNA double stranded breaks during SHM/CSR. In a physiological context, AID targets immunoglobulin (Ig) loci to mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID-initiated DNA lesions cannot be properly repaired. In this review, we focus on the molecular mechanisms that regulate the specificity of AID targeting and the repair pathways responsible for processing AID-initiated DNA lesions.

关键词： class switch recombination somatic hypermutation activation-induced deaminase DNA repair genomic instability

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Molecular simulation of the interaction mechanism between CodY protein and DNA in

Linchen Yuan, Hao Wu, Yue Zhao, Xiaoyu Qin, Yanni Li

《化学科学与工程前沿（英文）》 2019年第13卷第1期页码 133-139 doi: 10.1007/s11705-018-1737-4

摘要： In , the global transcriptional regulatory factor CodY can interact with the promoter DNA to regulate the growth, metabolism, environmental adaptation and other biological activities of the strains. In order to study the mechanism of interaction between CodY and its target DNA, molecular docking and molecular dynamics simulations were used to explore the binding process at molecular level. Through the calculations of the free energy of binding, hydrogen bonding and energy decomposition, nine key residues of CodY were identified, corresponding to SER184, SER186, SER208, THR217, ARG218, SER219, ASN223, LYS242 and GLY243, among which SER186, ARG218 and LYS242 play a vital role in DNA binding. Our research results provide important theoretical guidance for using wet-lab methods to study and optimize the metabolic network regulated by CodY.

关键词： CodY DNA molecular docking molecular dynamics

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Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications

null

《医学前沿（英文）》 2015年第9卷第3期页码 261-274 doi: 10.1007/s11684-015-0406-y

摘要：

Environmental pollution is one of the main causes of human cancer. Exposures to environmental carcinogens result in genetic and epigenetic alterations which induce cell transformation. Epigenetic changes caused by environmental pollution play important roles in the development and progression of environmental pollution-related cancers. Studies on DNA methylation are among the earliest and most conducted epigenetic research linked to cancer. In this review, the roles of DNA methylation in carcinogenesis and their significance in clinical medicine were summarized, and the effects of environmental pollutants, particularly air pollutants, on DNA methylation were introduced. Furthermore, prospective applications of DNA methylation to environmental pollution detection and cancer prevention were discussed.

关键词： environmental pollution DNA methylation cancer biomarker diagnosis therapy prevention

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Effects of DNA damage on oocyte meiotic maturation and early embryonic development

Shen YIN,Junyu MA,Wei SHEN

《农业科学与工程前沿（英文）》 2014年第1卷第3期页码 185-190 doi: 10.15302/J-FASE-2014035

摘要： DNA damage is one of the most common threats to meiotic cells. It has the potential to induce infertility and genetic abnormalities that may be passed to the embryo. Here, we reviewed exogenous factors which could induce DNA damage. Specially, we addressed the different effects of DNA damage on mouse oocytes and embryonic development. Complex DNA damage, double-strand breaks, represents a more difficult repair process and involves various repair pathways. Understanding the mechanisms involved in DNA damage responses may improve therapeutic strategies for ovarian cancer and fertility preservation.

关键词： DNA damage double-strand breaks (DSBs) oocyte embryo

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表征不同DNA高阶结构的单分子分析方法 Review

刘泳麟, 边天元, 刘岩, 李治民, 裴羽丰, 宋杰

《工程（英文）》 2023年第24卷第5期页码 277-292 doi: 10.1016/j.eng.2022.10.009

摘要：

DNA不仅是生命遗传信息的载体，而且是一种高度可编程和自组装的纳米材料。不同的DNA结构与其生物学和化学功能有关。因此，了解各种DNA结构的物理和化学性质在生物学和纳米化学中具有重要意义。然而，群体分子实验忽略了溶液中DNA结构的异质性。单分子分析方法是观察单个分子的行为和探测自由能态的高异质性的有力工具。本文介绍了单分子检测和操纵等单分子分析方法，并讨论了这些方法如何用于测量单/双链DNA（ss/dsDNA）、DNA高阶结构和DNA纳米结构的分子性质。最后，将DNA纳米技术和单分子分析方法进行结合以了解DNA和其他生物物质、软物质的生物物理特性。

关键词：单分子分析方法 DNA结构力学性能构象转变

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基于探针图的并行型图顶点着色DNA计算模型 Article

许进, 强小利, 张凯, 张成, 杨静

《工程（英文）》 2018年第4卷第1期页码 61-77 doi: 10.1016/j.eng.2018.02.011

摘要：

目前DNA 计算机研究中遇到的最大瓶颈是解空间指数爆炸问题，即随着问题规模的增大，所需要作为信息处理“数据”的DNA分子呈指数级增大。本文提出了一种新颖的图顶点着色DNA计算模型，该模型正是围绕着如何克服解空间指数爆炸问题以及如何提高运行速度而设计的。本文以一个3-着色的61 个顶点的图为例，实验表明，99% 的非可行解在构建初始解空间时就被删除，并利用DNA 自组装和并行PCR 方法，通过识别、拼接以及组装等技术得到解。

关键词： DNA计算图顶点着色问题聚合酶链反应（PCR）

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hydrophobic environment triggering reactive fluorescence probe to real-time monitor mitochondrial DNA

《化学科学与工程前沿（英文）》 2022年第16卷第1期页码 92-102 doi: 10.1007/s11705-021-2063-9

摘要： Mitochondrial DNA has a special structure that is prone to damage resulting in many serious diseases, such as genetic diseases and cancers. Therefore, the rapid and specific monitoring of mitochondrial DNA damage is urgently needed for biological recognition. Herein, we constructed an in situ hydrophobic environment-triggering reactive fluorescence probe named MBI-CN. The fluorophore was 2-styrene-1H-benzo[d]imidazole, and malononitrile was introduced as a core into a molecule to initiate the hydrolysis reaction in the specific environment containing damaged mitochondrial DNA. In this design, MBI-CN conjugates to mitochondrial DNA without causing additional damages. Thus, MBI-CN can be hydrolyzed to generate MBI-CHO in an in situ hydrophobic environment with mitochondrial DNA damage. Meanwhile, MBI-CHO immediately emitted a significative fluorescence signal changes at 437 and 553 nm within 25 s for the damaged mitochondria DNA. Give that the specific and rapid response of MBI-CN does not cause additional damages to mitochondrial DNA, it is a potentially effective detection tool for the real-time monitoring of mitochondrial DNA damage during cell apoptosis and initial assessment of cell apoptosis.

关键词： hydrolysis reaction mitochondrial DNA damage in situ hydrophobic environment trigger fluorescence probe apoptosis