The possibility has been proposed and studied, both theoretically and experimentally, of implementing an orthogonal system inside cells independent of the cellular genetic material in order to make a completely safe system, with the possible increase in encoding potentials.
Several groups have focused on different aspects:
* Novel backbones and base pairs as discussed above;
* XNA artificial replication and transcription polymerases starting generally from T7 RNA polymerase;
* (16S ribosomal sequences with altered anti-Shine-Dalgarno sequences allowing the translation of only orthogonal mRNA with a matching altered Shine-Dalgarno sequence; and
* Novel tRNA encoding non-natural aminoacids for an expanded genetic code.