SAN DIEGO, Nov. 29, 2017 /PRNewswire/ — Synthorx Inc. announced today that scientists at The Scripps Research Institute (TSRI) and the company, guided by Floyd Romesberg, Ph.D., have developed the first semi-synthetic organism that can store and retrieve increased genetic information. The semi-synthetic organism was made to maintain, replicate, transcribe, and translate a synthetic DNA base pair in order to incorporate various non-natural amino acids (nnAAs) into a full-length protein. This research, published today in Nature, breaks through technical barriers to creating more diverse proteins for improved drug characteristics as well as enabling cost-effective scale-up for drug development.
An expanded genetic alphabet allows for site-specific incorporation of different non-natural amino acids to create novel full-length and functional proteins. In the current paper, the scientists used the semi-synthetic organism to create a variant of green fluorescent protein (GFP) with non-natural amino acids incorporated at specific sites. The semi-synthetic organism was able to robustly produce the full-length variant protein with an efficiency similar to that with which the natural protein is produced.
Dr. Romesberg said, “This is the first time that proteins have been produced in any cell by the decoding of a six-letter genetic alphabet, instead of just the natural four-letter alphabet. The limited combinations of the natural DNA bases, A, T, G, and C, have restricted the types of new protein therapeutics that could be made. Adding X and Y to the genetic alphabet, we now have an expanded vocabulary to be able to generate a variety of new proteins that might be developed for a wide range of applications, including as new therapeutics.”
The regular ‘genetic alphabet’ of DNA constitutes of two base pairs (A–T and G–C). Dr. Romesberg and his team designed another base pair, d5SICSTP and dNaMTP (abbreviated X and Y), that was previously shown to be stably replicated and maintained by a single-celled organism. The four natural DNA bases are used to code for or “spell” proteins assembled from the 20 natural amino acids. With X and Y, it is now in principle possible to encode for an additional 152 novel amino acids to make proteins with unique pharmacological properties and to improve the safety and efficacy of protein therapeutics.
“Protein therapeutics have delivered tremendous value to patients, but have limitations that cannot be corrected utilizing the twenty natural amino acids,” said Laura Shawver, Ph.D., president and CEO of Synthorx. “Now that