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Bacterial therapies at the interface of synthetic biology and nanomedicine.
Literature Information
| DOI | 10.1038/s44222-023-00119-4 |
|---|---|
| PMID | 38962719 |
| Journal | Nature reviews bioengineering |
| Impact Factor | 37.6 |
| JCR Quartile | Q1 |
| Publication Year | 2024 |
| Times Cited | 23 |
| Keywords | Bacterial therapies, Synthetic biology, Nanomedicine, Controllable systems, Clinical translation |
| Literature Type | Journal Article |
| ISSN | 2731-6092 |
| Pages | 120-135 |
| Issue | 2(2) |
| Authors | Jaeseung Hahn, Suwan Ding, Jongwon Im, Tetsuhiro Harimoto, Kam W Leong, Tal Danino |
TL;DR
This paper reviews the potential of engineering bacteria as therapeutic agents, emphasizing their dual role as effective treatments and potential sources of toxicity due to their immunostimulatory nature. By integrating synthetic biology and nanomedicine, the authors discuss advancements in creating controllable bacterial systems that enhance safety and efficacy, while also addressing challenges for clinical application.
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Bacterial therapies · Synthetic biology · Nanomedicine · Controllable systems · Clinical translation
Abstract
Bacteria are emerging as living drugs to treat a broad range of disease indications. However, the inherent advantages of these replicating and immunostimulatory therapies also carry the potential for toxicity. Advances in synthetic biology and the integration of nanomedicine can address this challenge through the engineering of controllable systems that regulate spatial and temporal activation for improved safety and efficacy. Here, we review recent progress in nanobiotechnology-driven engineering of bacteria-based therapies, highlighting limitations and opportunities that will facilitate clinical translation.
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Primary Questions Addressed
- What specific disease indications have shown the most promise for treatment using bacterial therapies enhanced by synthetic biology and nanomedicine?
- How do the safety profiles of engineered bacteria compare to traditional therapeutic agents in clinical settings?
- In what ways can the spatial and temporal regulation of bacterial therapies improve their efficacy and reduce potential toxicity?
- What are the current limitations in the clinical translation of nanobiotechnology-driven bacterial therapies, and how might these be overcome?
- How does the integration of synthetic biology with nanomedicine enhance the immunostimulatory properties of bacterial therapies?
Key Findings
Research Background and Objectives
Bacteria are being explored as therapeutic agents for various diseases due to their unique properties as living drugs. While these therapies offer significant advantages, such as replication and immunostimulation, they also pose potential toxicity risks. The aim of this review is to examine the advancements in synthetic biology and nanomedicine that can enhance the safety and efficacy of bacteria-based therapies through controlled activation mechanisms.
Main Methods/Materials/Experimental Design
The review synthesizes recent literature on the engineering of bacteria using nanobiotechnology. The approach can be summarized in the following flowchart:
- Synthetic Biology Techniques: Various genetic engineering methods are employed to modify bacteria.
- Engineering Bacteria: Focus on creating bacteria that can be programmed for specific therapeutic functions.
- Controllable Systems: Development of systems that allow for spatial and temporal control over bacterial activity.
- Spatial Activation: Targeting bacteria to specific sites in the body.
- Temporal Activation: Controlling the timing of bacterial activity.
- Improved Safety and Enhanced Efficacy: The ultimate goal is to minimize toxicity while maximizing therapeutic benefits.
Key Results and Findings
- Advancements in Engineering: The review highlights successful strategies for modifying bacteria to enhance their therapeutic potential while mitigating risks.
- Nanobiotechnology Integration: The combination of nanotechnology with synthetic biology allows for more precise control over bacterial therapies.
- Clinical Translation Opportunities: Identifies several promising pathways for translating engineered bacteria into clinical applications, addressing both efficacy and safety concerns.
Main Conclusions/Significance/Innovation
The review underscores the transformative potential of integrating synthetic biology and nanomedicine in developing bacteria-based therapies. The engineering of controllable bacterial systems can significantly improve safety profiles and therapeutic outcomes, paving the way for clinical applications in treating a variety of diseases. This innovative approach may redefine how living drugs are utilized in medicine.
Research Limitations and Future Directions
- Limitations: The review acknowledges that while there are promising advancements, challenges remain in ensuring consistent and reliable control of bacterial therapies. Additionally, the long-term effects of engineered bacteria in human subjects are not yet fully understood.
- Future Directions:
- Further research is needed to optimize control mechanisms for bacterial activation.
- Studies should focus on the long-term safety and efficacy of these therapies in clinical settings.
- Exploration of additional disease indications that could benefit from bacteria-based treatments is encouraged.
| Section | Summary |
|---|---|
| Research Background | Bacteria as living drugs; potential toxicity; need for controlled therapies. |
| Main Methods/Design | Synthetic biology, nanotechnology; focus on controllable systems. |
| Key Results | Successful engineering strategies; integration with nanobiotechnology; clinical translation pathways. |
| Main Conclusions | Enhanced safety and efficacy through innovative engineering approaches. |
| Limitations & Future Directions | Need for consistent control; long-term effects unclear; further research on optimization and new applications. |
References
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Literatures Citing This Work
- Novel delivery systems for controlled release of bacterial therapeutics. - Nadia Zaragoza;Grace I Anderson;Stephanie Allison-Logan;Kirmina Monir;Ariel L Furst - Trends in biotechnology (2024)
- Exploiting bacteria for cancer immunotherapy. - Seong-Young Kwon;Hien Thi-Thu Ngo;Jinbae Son;Yeongjin Hong;Jung-Joon Min - Nature reviews. Clinical oncology (2024)
- Physiochemically and Genetically Engineered Bacteria: Instructive Design Principles and Diverse Applications. - Xia Lin;Rong Jiao;Haowen Cui;Xuebing Yan;Kun Zhang - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
- Towards Understanding Tumour Colonisation by Probiotic Bacterium E. coli Nissle 1917. - Georgette A Radford;Laura Vrbanac;Rebekah T de Nys;Daniel L Worthley;Josephine A Wright;Jeff Hasty;Susan L Woods - Cancers (2024)
- Dynamic Gene Expression Mitigates Mutational Escape in Lysis-Driven Bacteria Cancer Therapy. - Filippo Liguori;Nicola Pellicciotta;Edoardo Milanetti;Sophia Xi Windemuth;Giancarlo Ruocco;Roberto Di Leonardo;Tal Danino - Biodesign research (2024)
- Multi-level insights into the immuno-oncology-microbiome axis: From biotechnology to novel therapies. - Zheshun Pi;Weici Liu;Chenghu Song;Chuandong Zhu;Jiwei Liu;Lu Wang;Zhao He;Chengliang Yang;Lei Wu;Tianshuo Liu;Zijie Geng;Scott J Tebbutt;Ningning Liu;Yuan Wan;Faming Zhang;Wenjun Mao - iMeta (2024)
- Remolding the tumor microenvironment by bacteria augments adoptive T cell therapy in advanced-stage solid tumors. - Chaojie Zhu;Chao Liu;Qing Wu;Tao Sheng;Ruyi Zhou;En Ren;Ruizhe Zhang;Zhengjie Zhao;Jiaqi Shi;Xinyuan Shen;Zhongquan Sun;Zhengwei Mao;Kaixin He;Lingxiao Zhang;Yuan Ding;Zhen Gu;Weilin Wang;Hongjun Li - Signal transduction and targeted therapy (2024)
- Angiogenesis, a key point in the association of gut microbiota and its metabolites with disease. - Yan Wang;Mingshuai Bai;Qifan Peng;Leping Li;Feng Tian;Ying Guo;Changqing Jing - European journal of medical research (2024)
- Recent development of micro-nano carriers for oral antineoplastic drug delivery. - Hongzheng Li;Xiang Chen;Shangrui Rao;Minyu Zhou;Jianhua Lu;Danna Liang;Bingzi Zhu;Letian Meng;Ji Lin;Xiaoya Ding;Qingfei Zhang;Danhong Hu - Materials today. Bio (2025)
- Emerging Elastic Micro-Nano Materials for Diagnosis and Treatment of Thrombosis. - Chenxin Lu;Chunjian Li;Ning Gu;Fang Yang - Research (Washington, D.C.) (2025)
... (13 more literatures)
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