袁伯川, 金义光. 基于工程化细菌的活体生物药: 现状与未来J. 药学学报, 2025, 60(5): 1183-1196. DOI: 10.16438/j.0513-4870.2025-0139
引用本文: 袁伯川, 金义光. 基于工程化细菌的活体生物药: 现状与未来J. 药学学报, 2025, 60(5): 1183-1196. DOI: 10.16438/j.0513-4870.2025-0139
YUAN Bo-chuan, JIN Yi-guang. Living biotherapeutic products based on engineered bacteria: current status and future prospectsJ. Acta Pharmaceutica Sinica, 2025, 60(5): 1183-1196. DOI: 10.16438/j.0513-4870.2025-0139
Citation: YUAN Bo-chuan, JIN Yi-guang. Living biotherapeutic products based on engineered bacteria: current status and future prospectsJ. Acta Pharmaceutica Sinica, 2025, 60(5): 1183-1196. DOI: 10.16438/j.0513-4870.2025-0139

基于工程化细菌的活体生物药: 现状与未来

Living biotherapeutic products based on engineered bacteria: current status and future prospects

  • 摘要: 活体生物药(live biotherapeutic product, LBP) 是一类含有活性生物体(如细菌) 的用于预防或治疗人类疾病的生物制品(不包括疫苗)。目前LBP的研发主要聚焦于活细菌。LBP与传统药物相比具有可复制性、靶向性、响应性等特点, 成为多种重大疾病药物研发的热点, 适应症涉及恶性肿瘤、代谢性疾病、炎症性肠病、基因缺陷病等。由于天然细菌存在活性低、不稳定和安全性等问题, 对其进行工程化改造是改良细菌药物学特性、促进细菌向LBP应用转化的关键。本文详细调研了近年来基于工程化细菌的LBP研究进展, 总结了基于化学作用、物理作用、遗传改造的工程化策略, 发现单一途径的工程化细菌疗效、稳定性和安全性问题仍不能完全解决, 因此提出“多工程化细菌”(multi-engineered bacteria) 理念, 即通过物理、化学、生物的组合工程化提高细菌成药性。本文通过对基于工程化细菌的LBP研究进行综述, 为LBP研发提供前瞻性思考和展望。

     

    Abstract: Live biotherapeutic products (LBPs) represent a distinct category of biological products containing viable organisms, such as bacteria, utilized for the prevention and treatment of human diseases (excluding vaccines). Presently, research and development efforts in LBPs are predominantly centered on live bacteria. Compared to traditional drugs, the LBPs demonstrate unique characteristics, including replicability, target specificity, and responsiveness. Owing to these properties, LBPs have emerged as hotspots in the development of specialized treatments for various major diseases, with applications spanning malignant tumors, metabolic disorders, inflammatory bowel diseases, genetic defects, and more. Nevertheless, natural bacteria face inherent limitations—such as low activity, instability, and safety concerns—that hinder their pharmacological potential. As a result, engineering strategies have become essential for enhancing the properties of bacteria and facilitating their clinical applications. This article delves into recent advancements in LBPs derived from engineered bacteria, offering a systematic review of reported engineering strategies, which are broadly categorized into chemical, physical, and genetic modifications. The findings indicate that no single engineering approach can comprehensively address all the challenges associated with converting viable bacteria into effective LBPs. To overcome this limitation, a concept of "multi-engineered bacteria" is introduced. This framework advocates for the integration of physical, chemical, and biological engineering strategies to develop next-generation LBPs with enhanced functionality and clinical potential. This article provides a concise review of current research on LBPs based on engineered bacteria and outlines forward-looking perspectives for advancing their development through innovative engineering approaches.

     

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