RNA therapeutics offer transformative potential for neural repair. However, various delivery challenges continue to hinder the clinical translation of RNA therapeutics. Synthetic biology, as an interdisciplinary cutting-edge field, improves delivery systems by utilizing modular design and rational engineering. This approach leads to greater efficiency, precision, and programmability in these systems. This review addresses the application of synthetic biology-based bioinspired delivery systems for neural repair. First, this review outlines the challenges faced by RNA therapies in neural repair: systemic administration encounters challenges posed by the blood-brain barrier and blood-nerve barrier; local administration faces issues related to limited tissue penetration and diffusion; intranasal administration suffers from low efficiency; and clinical translation must also address safety concerns and the need for standardized production that complies with Good Manufacturing Practices. Second, this review describes bioinspired delivery strategies based on synthetic biology, which incorporate modular design, biomimetic synthesis, and biological engineering approaches. Third, this review introduces innovative applications of synthetic biology in drug delivery systems for neural repair, guided by the Design-Build-Test-Learn cycle. This cycle connects fundamental biological mechanisms with artificial intelligence-assisted computational tools to optimize formulations while managing the complexities of deploying biological circuits in the central nervous system. Fourth, this review evaluates the landscape of clinical translation by drawing on insights from commercial products and clinical trials. It considers important factors such as Chemistry, Manufacturing, and Controls requirements, platform-based regulatory pathways, and ethical issues related to engineered cell therapies. Finally, this review offers a perspective on the potential of synthetic biology-based RNA therapeutics in neural repair, emphasizing significant technical innovations. Three primary challenges that can be addressed are identified: (1) overcoming central nervous system delivery challenges through the design of synthetic biology; (2) translating mechanistic insights into practical applications using the Design-Build-Test-Learn framework; and (3) aligning new delivery methods with complex regulatory pathways. The primary contribution of this review is the creation of a system engineering framework that converts RNA delivery into programmable biological machines. This framework emphasizes the Design-Build-Test-Learn cycle and incorporates artificial intelligence-assisted tools, thereby advancing the field of central nervous system delivery technologies, particularly in neural repair.
Shen et al. (Thu,) studied this question.