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Cell, February 05, 2025 | https://doi.org/10.1016/j.cell.2025.01.017
Engineered commensals for targeted nose-to-brain drug delivery
Haosheng Shen,1,2,3,4 Nikhil Aggarwal,1,2,3,4 Beiming Cui,5 Guo Wei Foo,1,2,3,4 Yuanzhi He,1,2,3,4 Santosh Kumar Srivastava,1,2,3,4 Shengjie Li,1,2,3,4,6 Marcus Ze Xian Seah,1,2,3 Kwok Soon Wun,1,2,3,4 Hua Ling,1,2,3,8 In Young Hwang,1,2,3,9 Chun Loong Ho,5 Yung Seng Lee,1,2,7 and Matthew Wook Chang 1,2,3,4,10,*
1NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore
2Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
3Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
4National Centre for Engineering Biology (NCEB), Singapore, Singapore
5Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, China
6Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, China
7Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
8Present address: Wilmar International Limited, Singapore, Singapore
9Present address: Food, Chemical, and Biotechnology, Singapore Institute of Technology, Singapore, Singapore
10Lead contact
2Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
3Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
4National Centre for Engineering Biology (NCEB), Singapore, Singapore
5Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, China
6Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, China
7Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
8Present address: Wilmar International Limited, Singapore, Singapore
9Present address: Food, Chemical, and Biotechnology, Singapore Institute of Technology, Singapore, Singapore
10Lead contact
*Corresponding author: correspondence to Matthew Wook Chang
Abstract
Intranasal administration through the olfactory epithelium (OE) presents a direct pathway for brain-targeted therapeutic delivery, although its feasibility is hampered by the anatomical and absorptive limitations of the OE. In this study, we identified Lactobacillus plantarum WCFS1 (Lp), a commensal strain with a natural affinity for the OE and engineered it to function as a vector for cerebral drug delivery. Upon intranasal administration, Lp released specific payload molecules within the OE, with subsequent transport and accumulation in the brain. The therapeutic efficacy of Lp was further validated by the recombinant production and secretion of appetite-regulating hormones. When administered intranasally in a murine model of obesity prevention, the engineered Lp significantly alleviated obesity-related symptoms. This was evidenced by decreased appetite, reduced body weight gain, and improved glucose metabolism and fat mass deposition. Our study demonstrates the capability of Lp as an intranasal delivery vehicle, emphasizing its potential for brain-targeted therapeutic applications.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-06)
- 국외 연구진
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