Biorthogonal translation system for production of pharmaceuticals during space missions

Access to means of production for pharmaceutical compounds remains a challenge for long term space travel. Cell free protein synthesis (CFPS) systems are stable, modular, light weight, and require only the addition of water to activate. The stability of these systems could be further increased by using phosphorothioate deoxyribonucleic acid (PS-DNA) and phosphorothioate ribonucleic acids (PS-RNA). These modified nucleic acids are nuclease resistant, and bio-contained (orthogonal to natural nucleic acids). This proposal develops phosphorothioate transfer ribonucleic acids (PS-tRNAs), and phosphorothioate flexizymes (PS-flexizymes), enzymes capable of amino acylating tRNAs with a diverse array of unnatural amino acids, for the use in CFPS systems. Then the long-term stability and nuclease resistance of the CFPS will be investigated, first using phosphorothioate messenger ribonucleic acid (PS-mRNA) templates, which we have shown can be translated (unpublished preliminary data), and then expanding to the other PS nucleic acids developed in this proposal. The resulting system will be bio-contained, nuclease resistant, and stable for several years. This platform will enable production of medicinal peptides and proteins on demand, under low resource conditions like space flight. Due to the flexible and modular nature of the system, this technology could also be developed into a versatile platform for in situ advanced material manufacturing during space flight.

This is a mature technology (TRL 7+) — the realistic path in is usually NASA's Technology Transfer Program: licensing an existing NASA patent, or a Space Act Agreement to use NASA facilities/expertise directly. NASA also runs a startup licensing program with no upfront fee for companies formed to commercialize a specific NASA technology.

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