While DNA, RNA, and proteins containing natural building blocks are readily synthesized using natural biological machinery and the rules of templated biosynthesis, DNA, RNA, and proteins containing modified or unnatural building blocks, including ones that recapitulate post-translational modifications, are difficult to access. Only certain unnatural building blocks are available, only a few distinct unnatural building blocks can be used simultaneously, and the length of fully unnatural polymers that can be produced is extremely low compared to natural counterparts. Overcoming these bottlenecks will lead to new biomolecules with expanded functions stemming from the diversity of non-canonical and unnatural building blocks that could become available to synthetic biology.
The design, generation, and evolution of macromolecules containing unnatural building blocks relies on the achievement of the same capabilities as the production of wholly-natural macromolecules. This Goal reflects the special considerations necessary for the utilization of unnatural building blocks.
Breakthrough Capabilities & Milestones
PCR, reverse transcription, cellular replication, and transcription of fully unnatural nucleotide-containing genes of up to 400 base pairs.
At this length, unnatural aptamer and aptazyme polymers could be regularly evolved and engineered.