Throughout the last 21 years of the iGEM competition, the Selenocysteine Insertion Sequence (SECIS) has not once been the focus of an iGEM project. As a matter of fact, no project before has revolved on the study and implementation of STOP codon readthroughs, whatsoever. They have only been used occasionally in experiments to test other parts.
It is undeniable that SKIPPIT is the first of its kind in the iGEM competition, and that it is paving the way to a new approach of controlling protein expression, through unique control of translation. We are pushing boundaries that the iGEM competition did not even know existed.
We are the first team to publish the SECIS sequence to the iGEM registry. This part is so intricate and unique in its functionality and activity, that we needed the iGEM registry team to add a new “type” to better classify this part. It is, after all, a 3’-UTR sequence that regulates ribosomal function.
Although hundreds of teams have developed RNA switches and riboswitches, only some have been able to code their own software model to design them, and even less have had the time to test their creation in the wet lab. At SKIPPIT we have been able to do all of the above in human cells, to add to its complexity. The result has been the creation of a swich that allows the user to control a STOP codon readthrough’s activity, with a dual-protein regulatory approach. This swich is particularly special due to how far the swich sequence can be from its action site. This means that the swich doesn’t need to be translated to perform its function, and that it will not affect the protein sequence. To highlight just how innovative this technology is, there is no previous literature describing the existence of a STOP codon readthrough RNA switch.
We hope that our project can inspire many of the future iGEM teams to push the boundaries of what is known, and to create brand new technologies that define the future of synthetic biology.