Synthetic Biology-Inspired Biocontainment Strategies of Therapeutic Genetically Engineered Bacteria

ABSTRACT: With the rapid expansion of synthetic gene technologies and engineered bacteria for disease diagnosis or therapy, biosafety concerns have intensified. Substantial efforts have therefore been directed toward developing biocontainment systems that prevent the unintended release of engineered microorganisms and the horizontal transfer of synthetic genetic elements into natural ecosystems. Recent advances in synthetic biology have yielded a diverse suite of biocontainment strategies, including engineered biosafety genetic circuits, genetic isolation approaches, targeted degradation of genetic material, and physical encapsulation of microbial chassis. Furthermore, the incorporation of unnatural nucleic acids and noncanonical amino acid-based orthogonal replication, transcription, and translation systems has markedly improved the robustness and orthogonality of these containment platforms. In this review, we summarize the latest developments in biocontainment strategies for genetically engineered bacteria and discuss how these innovations may address current and emerging biosafety challenges.