合成生物学的医学应用研究进展 相对于其他治疗方式,合成生物学诊疗涉及一些新的伦理8 Wang S, Dos- SantosALA, Huang w,eta. Driving mosquito 与安全问题。2016年,美国FDA出台了一份指南,明 refractoriness to Plasmodium falciparum with engineered 确阐明了一些以食物或膳食补充剂合法问世的活性生物 symbiotic bacteria. Science, 2017, 357(6358): 1399-1402 疗法产品( live biotherapeutic product,LBP)能怎样被用9siL,xulH, Zhou X,etal. Generation of influenza a viruses as 于研究,并解释了研究人员在早期临床试验中,要满足 live but replication-incompetent virus vaccines. Science, 2016 怎样的生产要求,才能将益生菌当作药物。 354(6316):1l70-1173 我国在这方面的监管仍需加快布局,确保在现有的10 Li P Ke x, Wang T,etal. Zika virus attenuation by codon pair 监管体系内建立起现代、高效的评估政策。一方面充分 deoptimization induces sterilizing immunity in mouse model 发挥活性生物疗法产品的潜在益处,另一方面也了解其 Journal of Virology, 2018, 92(17). pii: c00701-18 中的特定风险。合成生物诊疗产品还需要更多的研发, 1 Piotr wnuk. Oncolytics: the dawn of a new era in cancer treatment. 需要精心设计的临床试验来确保这些产品的安全性与有 [2018-08-02].https://pharmaphorum.com/views-and-analysis/ 效性,从而释放合成生物学在医学应用中的潜力,造福 个体与公众健康。 12吴蓉。首例超级细菌感染患者经噬菌体治疔痊愈.[2018-08- 15]http://www.sh.chinanews.com/yljk/2018-08-15/43418.shtml. 参考文献 13 Associated Press. Second man undergoes gene editing: Therapy I Richardson M A, Ramirez T, Russell N C, et al. Coley toxins hasnosafetyflagssofar.[2018-02-06].https://www.voanews amunotherapy: a retrospective review. Alternative Therapies in com/a/second-man-undergoes-gene-editing/4242428 html Health and Medicine, 1999, 5(3): 42. 14医麦克.潜心研究ZFN基因编耨技术20年 Sangamo公司 2 Forbes, N. S. Engineering the perfect(bacterial) cancer therapy 成为行业领导者[2018-07-30].http://med.sinacom/article Nature Reviews Cancer, 2010, 10(11): 785. detail 103 2 49638 html 3 Yu B, Yang M, Shi L, et al. Explicit hypoxia targeting with tumor 15 Tom Ireland. I want to help humans genetically modify themselve bic salmonella [2017-12-24].https://www.theguardian.com/science/2017/dec/24/ Typhimurium strain Scientific Reports, 2012, 2: 436. josiah-zayner-diy-gene-editing-therapy-crispr-interview 4 Danino T, Prindle A, Kwong G A, et al. Programmable probiotics 16 Liu Y, Zeng Y, Liu L, et al. Synthesizing AND gate genetic circuits for detection of cancer in urine. Science Translational Medicine based on crisPr-Cas9 for identification of bladder cancer cells 015,7(289):289na84 Nature Communations. 2014.5: 5393. 5 Din M O, Danino T, Prindle A, et al. Synchronized cycles of 17 Roybal K T, Lim WA Synthetic immunology: hacking immune bacterial lysis for in vivo delivery. Nature, 2016, 536(7614): 81-85 cells to expand their therapeutic capabilities. Annual Reviews of 6 Sheth R U, Yim SS, Wu F L, et al. Multiplex recording of cellular Immunology,2017,35:229-253 events over time on CRISPR biological tape. Science, 2017, 18 Nissim L, Wu MR, Pery E, et al, Synthetic RNA-based 358(6369):1457-1461 immunomodulatory gene circuits for cancer immunotherapy. Cell 7 Mimee M, Nadeau P, Hayward A, et al. An ingestible bacterial- 2017,171(5):1138-1150. electronic system to monitor gastrointestinal health Science, 2018, 19 Xie M, Ye H, Wang H, et al. B-cell-mimetic designer cells provide 360(6391):915-91 closed-loop glycemic control. Science, 2016, 354(6317): 1296- ③中阉钾院院刊|125院刊 1225 合成生物学的医学应用研究进展 相对于其他治疗方式，合成生物学诊疗涉及一些新的伦理 与安全问题。2016 年，美国 FDA 出台了一份指南[30]，明 确阐明了一些以食物或膳食补充剂合法问世的活性生物 疗法产品（live biotherapeutic product，LBP）能怎样被用 于研究，并解释了研究人员在早期临床试验中，要满足 怎样的生产要求，才能将益生菌当作药物。 我国在这方面的监管仍需加快布局，确保在现有的 监管体系内建立起现代、高效的评估政策。一方面充分 发挥活性生物疗法产品的潜在益处，另一方面也了解其 中的特定风险。合成生物诊疗产品还需要更多的研发， 需要精心设计的临床试验来确保这些产品的安全性与有 效性，从而释放合成生物学在医学应用中的潜力，造福 个体与公众健康。 参考文献 1 Richardson M A, Ramirez T, Russell N C, et al. Coley toxins immunotherapy: a retrospective review. Alternative Therapies in Health and Medicine, 1999, 5(3): 42. 2 Forbes, N. S. Engineering the perfect (bacterial) cancer therapy. Nature Reviews Cancer, 2010, 10(11): 785-794. 3 Yu B, Yang M, Shi L, et al. Explicit hypoxia targeting with tumor suppression by creating an “obligate” anaerobic Salmonella Typhimurium strain. Scientific Reports, 2012, 2: 436. 4 Danino T, Prindle A, Kwong G A, et al. Programmable probiotics for detection of cancer in urine. Science Translational Medicine, 2015, 7 (289): 289ra84. 5 Din M O, Danino T, Prindle A, et al. Synchronized cycles of bacterial lysis for in vivo delivery. Nature, 2016, 536(7614): 81-85. 6 Sheth R U, Yim S S, Wu F L, et al. Multiplex recording of cellular events over time on CRISPR biological tape. Science, 2017, 358(6369): 1457-1461. 7 Mimee M, Nadeau P, Hayward A, et al. An ingestible bacterial￾electronic system to monitor gastrointestinal health. Science, 2018, 360(6391): 915-918. 8 Wang S, Dos-Santos A L A, Huang W, et al. Driving mosquito refractoriness to Plasmodium falciparum with engineered symbiotic bacteria. Science, 2017, 357(6358): 1399-1402. 9 Si L, Xu H, Zhou X, et al. Generation of influenza A viruses as live but replication-incompetent virus vaccines. Science, 2016, 354(6316): 1170-1173. 10 Li P, Ke X, Wang T, et al. Zika virus attenuation by codon pair deoptimization induces sterilizing immunity in mouse models. Journal of Virology, 2018, 92(17). pii: e00701-18. 11 Piotr Wnuk. Oncolytics: the dawn of a new era in cancer treatment. [2018-08-02]. https://pharmaphorum.com/views-and-analysis/ oncolytics-new-era-cancer-treatment/. 12 吴蓉. 首例超级细菌感染患者经噬菌体治疗痊愈. [2018-08- 15]. http://www.sh.chinanews.com/yljk/2018-08-15/43418.shtml. 13 Associated Press. Second man undergoes gene editing; Therapy has no safety flags so far. [2018-02-06]. https://www.voanews. com/a/second-man-undergoes-gene-editing/4242428.html. 14 医麦克. 潜心研究ZFN基因编辑技术20年 Sangamo公司 成为行业领导者. [2018-07-30]. http://med.sina.com/article_ detail_103_2_49638.html. 15 Tom Ireland. I want to help humans genetically modify themselves. [2017-12-24]. https://www.theguardian.com/science/2017/dec/24/ josiah-zayner-diy-gene-editing-therapy-crispr-interview. 16 Liu Y, Zeng Y, Liu L, et al. Synthesizing AND gate genetic circuits based on CRISPR-Cas9 for identification of bladder cancer cells. Nature Communations, 2014, 5: 5393. 17 Roybal K T , Lim W A. Synthetic immunology: hacking immune cells to expand their therapeutic capabilities. Annual Reviews of Immunology, 2017, 35: 229-253. 18 Nissim L, Wu M R, Pery E, et al. Synthetic RNA-based immunomodulatory gene circuits for cancer immunotherapy. Cell, 2017, 171(5): 1138-1150. 19 Xie M, Ye H, Wang H, et al. β-cell-mimetic designer cells provide closed-loop glycemic control. Science, 2016, 354(6317): 1296-