Kim Wonhee, Han Jinjoo, Chauhan Shraddha, Lee Jeong Wook
Division of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, 37673, Korea.
Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, 37673, Korea.
J Biol Eng. 2025 Jun 5;19(1):55. doi: 10.1186/s13036-025-00523-x.
The convergence of cell-free protein synthesis (CFPS) and vesicle-based delivery platforms presents a promising avenue for therapeutic development. The open environment of CFPS offers precise control over protein synthesis by enabling the modulation of synthetic conditions. Additionally, vesicle-based platforms provide enhanced stability, bioavailability, and targeted delivery. This synergy facilitates the efficient production of complex proteins-including membrane proteins, antibody fragments, and proteins requiring post-translational modifications (PTMs)-and supports novel drug delivery strategies. While existing reviews have covered synthetic cells and biomanufacturing broadly, a dedicated analysis of CFPS system-containing vesicles (CFVs) for therapeutic applications remains absent from the literature. This review addresses this knowledge gap by providing a comprehensive examination of CFVs, highlighting their potential as programmable drug delivery platforms through the integration of genetic circuits. It emphasizes the advantages of CFPS over traditional cell-based approaches and explores the synergistic benefits of combining CFPS with various vesicle systems. These systems offer dynamic control over therapeutic protein production and targeted delivery, enabling precise responses to specific signals in complex environments. Although challenges such as low protein yield and imperfect targeting remain, potential optimization strategies are discussed. This analysis highlights the significant potential of integrating CFPS and vesicle-based delivery to advance biomanufacturing, therapeutic development, and synthetic cell systems, thereby opening new avenues in medicine and healthcare.
无细胞蛋白质合成（CFPS）与基于囊泡的递送平台的融合为治疗学发展提供了一条充满前景的途径。CFPS的开放环境通过调节合成条件实现对蛋白质合成的精确控制。此外，基于囊泡的平台具有更高的稳定性、生物利用度和靶向递送能力。这种协同作用有助于高效生产复杂蛋白质，包括膜蛋白、抗体片段以及需要进行翻译后修饰（PTM）的蛋白质，并支持新型药物递送策略。虽然现有综述广泛涵盖了合成细胞和生物制造，但文献中仍缺乏对用于治疗应用的含CFPS系统的囊泡（CFV）的专门分析。本综述通过全面考察CFV来填补这一知识空白，强调其通过整合遗传电路作为可编程药物递送平台的潜力。它强调了CFPS相对于传统基于细胞方法的优势，并探讨了将CFPS与各种囊泡系统相结合的协同益处。这些系统可对治疗性蛋白质生产和靶向递送进行动态控制，从而在复杂环境中对特定信号做出精确反应。尽管仍然存在蛋白质产量低和靶向不完善等挑战，但也讨论了潜在的优化策略。这一分析突出了整合CFPS和基于囊泡的递送以推进生物制造、治疗学发展和合成细胞系统的巨大潜力，从而为医学和医疗保健开辟新途径。
