小柯机器人

一个可编程的封装系统能改善治疗性细菌在小鼠体内的输送情况
2022-03-20 16:27

美国哥伦比亚大学Tal Danino、Kam W. Leong等研究人员合作开发出一个可编程的封装系统,能够改善治疗性细菌在小鼠体内的输送情况。相关论文于2022年3月17日在线发表在《自然—生物技术》杂志上。

研究人员开发了一个基因编码的微生物封装系统,该系统具有可调控和动态表达的表面囊状多糖,可增强全身性的传递。基于胶囊生物合成途径的小RNA筛选,研究人员构建了可诱导的合成基因回路,可调节大肠杆菌Nissle 1917中的细菌封装。这些细菌能够暂时躲避免疫攻击,而随后失去封装则会导致体内的有效清除。这种动态传递策略使细菌的最大耐受剂量增加了10倍,并提高了小鼠癌症模型的抗肿瘤效果。

此外,原位封装增加了微生物在小鼠肿瘤中的转位,从而产生远端肿瘤的疗效。可编程封装系统有望提高活体工程细菌对癌症的治疗效用。

据悉,活菌疗法已被提议作为治疗各种癌症的替代方法。

附:英文原文

Title: A programmable encapsulation system improves delivery of therapeutic bacteria in mice

Author: Harimoto, Tetsuhiro, Hahn, Jaeseung, Chen, Yu-Yu, Im, Jongwon, Zhang, Joanna, Hou, Nicholas, Li, Fangda, Coker, Courtney, Gray, Kelsey, Harr, Nicole, Chowdhury, Sreyan, Pu, Kelly, Nimura, Clare, Arpaia, Nicholas, Leong, Kam W., Danino, Tal

Issue&Volume: 2022-03-17

Abstract: Living bacteria therapies have been proposed as an alternative approach to treating a broad array of cancers. In this study, we developed a genetically encoded microbial encapsulation system with tunable and dynamic expression of surface capsular polysaccharides that enhances systemic delivery. Based on a small RNA screen of capsular biosynthesis pathways, we constructed inducible synthetic gene circuits that regulate bacterial encapsulation in Escherichia coli Nissle 1917. These bacteria are capable of temporarily evading immune attack, whereas subsequent loss of encapsulation results in effective clearance in vivo. This dynamic delivery strategy enabled a ten-fold increase in maximum tolerated dose of bacteria and improved anti-tumor efficacy in murine models of cancer. Furthermore, in situ encapsulation increased the fraction of microbial translocation among mouse tumors, leading to efficacy in distal tumors. The programmable encapsulation system promises to enhance the therapeutic utility of living engineered bacteria for cancer. Transient capsule induction allows engineered bacteria to evade initial immune surveillance in a colorectal cancer model.

DOI: 10.1038/s41587-022-01244-y

Source: https://www.nature.com/articles/s41587-022-01244-y

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:68.164
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex


本期文章:《自然—生物技术》:Online/在线发表

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