LAUSR

The near-universal genetic code defines the correspondence between codons in genes and amino acids in proteins. We refactored the structure of the genetic code in Escherichia coli and created orthogonal genetic codes that restrict the escape of synthetic genetic information into natural life. We developed orthogonal and mutually orthogonal horizontal gene transfer systems, which permit the transfer of genetic information between organisms that use the same genetic code but restrict the transfer of genetic information between organisms that use different genetic codes. Moreover, we showed that locking refactored codes into synthetic organisms completely blocks invasion by mobile genetic elements, including viruses, which carry their own translation factors and successfully invade organisms with canonical and compressed genetic codes. Description Changing the genetic code’s structure The genetic code, the rules by which genetic information is encoded in genes within DNA, is nearly universal across all kingdoms of life, enabling the transfer of genetic information and innovation between diverse cells. Biologists have long made use of the common code for engineering microbes, crops, and animals. Zürcher et al. permuted the rules by which genetic information is encoded in DNA and thereby created genetically isolated organisms that cannot exchange functional genetic information with other organisms. This provides a new paradigm that both protects valuable engineered organisms from natural invaders and safeguards the natural world from engineered genetic material. —DJ Genetic code refactoring in Escherichia coli enables genetic isolation and extends resistance to mobile genetic elements.