中国药物警戒 ›› 2025, Vol. 22 ›› Issue (1): 58-66.
DOI: 10.19803/j.1672-8629.20240271

• 基础与临床研究 • 上一篇    下一篇

治疗性DNA疫苗小鼠体内生物分布研究

侯田田1, 王旭东2,∆, 杨萍2, 周鹏博1, 秦超1, 黄瑛1, 王爱玲3, 耿兴超1, 周晓冰1,*, 刘德芳2#   

  1. 1中国食品药品检定研究院国家药物安全评价监测中心,药物非临床安全评价研究北京市重点实验室,北京 100176;
    2诺未科技（北京）有限公司,北京 100176;
    3北京华泰博奥生物科技有限公司,北京 102206
  • 收稿日期:2024-04-28 出版日期:2025-01-15 发布日期:2025-01-22
  • 通讯作者: *周晓冰,女,博士,研究员,药物临床前安全性评价。E-mail: zhxb@nifdc.org.cn。#为共同通信作者。
  • 作者简介:侯田田,女,硕士,助理研究员,药物临床前安全性评价。△为并列第一作者。
  • 基金资助:
    国家科技重大专项重大新药创制（2018ZX09201-017）; 药品监管科学全国重点实验室“mRNA药物非临床安全性评价新方法研究”; 北京市科技新星计划资助项目（Z211100002121008）

Biodistribution of Therapeutic DNA Vaccines in Mice

HOU Tiantian1, WANG Xudong2,∆, YANG Ping2, ZHOU Pengbo1, QIN Chao1, HUANG Ying1, WANG Ailing3, GENG Xingchao1, ZHOU Xiaobing1,*, LIU Defang2#   

  1. 1National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing Key Laboratory for Safety Evaluation of Drugs, Beijing 100176, China;
    2Newish Technology Co., Ltd, Beijing 100176, China;
    3Beijing, HuataiBoao Biotechnology Co., Ltd, Beijing 102206, China
  • Received:2024-04-28 Online:2025-01-15 Published:2025-01-22

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摘要： 目的 评估治疗性DNA疫苗在小鼠体内的分布及清除情况。方法 共使用156只C57BL/6N小鼠,分为阴性对照组、鼠源DNA疫苗组和人源DNA疫苗组,单次肌内注射给予小鼠,在给药后2、24 h,7、14、28、56 d解剖,取脏器,采用实时定量聚合酶链反应（Real-Time Quantitative PCR,qPCR）方法检测2种DNA疫苗在不同脏器的分布情况。结果 鼠源DNA疫苗和人源DNA疫苗在给予C57BL/6N小鼠后,给药后2 h,基因拷贝数最高,并广泛分布于各组织脏器,其中以注射部位含量最高,后各组织脏器基因拷贝数呈逐渐下降趋势。至给药后14 d,基因拷贝数在各组织脏器水平较低,与给药后24 h相比,约下降了99.9%以上。雌性和雄性分布趋势一致。在血液中,给药后2 h基因拷贝数水平较高,至给药后24 h,人源DNA疫苗和鼠源DNA疫苗已基本在血液中清除。结论 C57BL/6N小鼠肌内注射后2 h,鼠源DNA疫苗和人源DNA疫苗在各组织脏器广泛分布,以注射部位分布最高,且在体内存续时间不超过56 d。

关键词: 治疗性疫苗, 人源DNA疫苗, 鼠源DNA疫苗, 临床前研究, 小鼠, 生物分布, 实时定量聚合酶链反应, 分析方法验证

Abstract: Objective To evaluate the distribution and clearance of therapeutic DNA vaccines in mice Methods A total of 156 C57BL/6N mice were divided into the negative control group, mouse-derived DNA vaccine group and human-derived DNA vaccine group. Mice were given a single intramuscular injection. At 2 h, 24 h, 7 d, 14 d, 28 d and 56 d after administration, the mice were dissected and organs were collected. The distribution of the two DNA vaccines in different organs was detected using the real-time quantitative polymerase chain reaction (qPCR) method. Results After the administration of the mouse-derived DNA vaccine and human-derived DNA vaccine to C57BL/6N mice, the gene copy number peaked at 2 h and was widely distributed across tissues, among which the copy number at the injection site was the highest. Then, the gene copy number in various tissues and organs trended downward. At 14 d after administration, the gene copy number in various tissues and organs was low, with a decrease of approximately 99.9% compared to 24 h. The distribution was consistent between males and females. In blood, the gene copy number was high at 2 h, and by 24 h,the human-derived and mouse-derived DNA vaccine was basically cleared. Conclusion Two hours after intramuscular injection in C57BL/6N mice, the mouse-derived DNA vaccine and human-derived DNA vaccine are widely distributed in various tissues and organs, with the highest distribution at the injection site, and their survival time in the body does not exceed 56 d.

Key words: Therapeutic Vaccine, Human-Derived DNA Vaccine, Mouse-Derived DNA Vaccine, Preclinical Research, Mice, Biodistribution, Real-time Quantitative Polymerase Chain Reaction, Validation of Analytical Procedures

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