December 11, 2017

In light of recent advancements in the field of synthetic biology, defined loosely as the application of engineering principles to biological systems, in a series of posts we will be exploring the latest technology and discussing issues related to 101 rejections, such as whether one can own or patent synthetic organisms and/or the products generated from such organisms.  How these questions are answered will shape the future of the field, and will impact whether synthetic biology lives up to its enormous potential.

Life on earth is essentially a story about DNA, and the proteins encoded by DNA, which carry out the innumerable molecular reactions that support life itself at every level.  In a nutshell, DNA is a macromolecule with structural similarities to a common double-stranded “zipper”, comprising four base units that form base pairs ((adenine pairs with thymine, cytosine pairs with guanine).  This double-stranded nature of DNA enables instructions stored in a DNA to b­­e transcribed into a single stranded molecule termed messenger RNA, which is then translated into a particular protein according to the instructions. The building blocks of proteins consist of only 20 amino acids.  In other words, all complex life forms are the result of only 2 base pairs encoding proteins comprised of some variation of the 20 amino acids.  The sequence of amino acids for each particular protein is what dictates its molecular three dimensional structure, which relates to the particular function.  As an example, proteins in the brains of vertebrates called dopamine receptors are involved in neurological processes including cognition, memory, learning, pleasure, motivation, etc.
                Each protein’s three dimensional structure represents a remarkable example of molecular engineering.  A holy grail of molecular biology thus represents the possibility that particular desired proteins could be engineered to have unique functions, outside of what life has provided.  Such an ability would pave the way for medical advances to treat disease via protein therapeutics, or particular organisms could be created to carry out functions their counterparts cannot, such as producing biofuel, for example.
                The problem is that the translation of protein from RNA molecules is based on three-base sequences termed “codons”, where each codon corresponds to a particular amino acid.  So, if each codon corresponds to a particular amino acid, how to encode other unnatural amino acids?  One option is to reprogram particular codons (codons that otherwise encode for “stopping” or finishing the protein being generated) to accept unnatural amino acids.  Another option includes chemically synthesizing a stretch of amino acids where the stretch includes a desired unnatural amino acid, and then using molecular strategies to incorporate the chemically-synthesized stretch into a protein.  In my work as a scientist at Oregon Health Sciences University, I have experience doing both, and thus have first-hand knowledge of the challenges that need to be overcome to engineer proteins and in some examples organisms with new functionality.  However, the above-described approaches are extremely limited in their potential to realize the downstream applications such as those discussed above.
                Thus, in very exciting news this past week a major milestone was reported in the journal Nature http://www.nature.com/articles/nature24659 by scientists in San Diego.   In the report it was shown that a microbe that included instructions to synthesize proteins that include molecules never before used by any life form on earth, could live, reproduce, and synthesize such proteins.  Hailed as a major technical breakthrough, the results pave the way for a potential future where organisms that can synthesize designer proteins useful for widespread applications is a possibility.  The work is part of an ongoing effort that has led to a company Synthoryx, founded by the senior author of the above-mentioned publication, Floyd Romesburg.  The company has filed patent applications that are in various stages of prosecution at the current time.
                With the enormous potential of such developments, as discussed above we will be exploring the technology behind this landmark report, and the legal issues and implications surrounding such technology, in future posts.  Stay tuned!

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