A Programmable Finite-Replicated Organism Framework for Balanced Safety and Functionality.

ABSTRACT: Live-attenuated vaccines face a critical challenge in balancing immunogenicity with safety. To address this, we engineered programmable finite-replicated organisms (FROs) by depositing a limited number of indispensable components (such as noncanonical amino acids, ncAAs) within the cell, consuming the coenabling precise control of bacterial replication capability while preserving antigenic breadth. Two strategies were adopted to achieve the following purposes: (1) encoding ncAA in essential genes; (2) encoding ncAA in antitoxin of toxin-antitoxin (TA) systems. As noncanonical amino acids, 3,5-dichlorotyrosine (Cl2Y) was encoded by the amber codon (TAG) and inserted into the essential genes (e.g., serS, murG, and dnaA) or antitoxin genes. After optimizing expression and

SUBMITTER: Wang M 

PROVIDER: S-EPMC12471649 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature