Abstract Biological resources, such as sequence information, genetic traits, materials and strains, pose risks when inadvertently released or deliberately misused. To address these concerns, we developed Quadruplet COdon DEcoding (QCODE), a versatile genetic biocontainment strategy that introduces a quadruplet codon (Q-codon) causing frameshifts, hindering proper gene expression. Strategically incorporating Q-codons in multiple genes prevents genetic trait escape, unallowed proliferation of microbial strains and unauthorized leakages of genetic materials. This multifaceted strategy, integrating Q-codons for genetic traits, materials and strains, ensures robust biocontainment across various levels. Notably, our system maintains sequence protection, safeguarding genetic sequence information against unauthorized access. The QCODE approach offers a versatile, efficient and compact solution to enhance biosecurity in diverse biological research settings.

Quadruplet codon decoding-based versatile genetic biocontainment system