Synthetic DNA and Living Computers

This post is the second in a series exploring biocomputers. The first looked at whether biological computers could become a reality. Now I want to talk about synthetic DNA and how that might lead to living computers or living robots.

Natural DNA, or deoxyribonucleic acid, is two ribbons of nucleotides bound together and wound into the famed double helix. Nucleotides are made of a base molecule called a nucleobase plus a sugar called deoxyribose and a phosphate group. There are only four different bases in natural DNA: adenine (A); thymine (T); cytosine(C) and guanine (G). Here’s a really fun video on how DNA works from http://www.statedclearly.com:

In the last few years scientists have been racing to expand the DNA alphabet with unnatural DNA bases. Two of these, d5SICS and dNaM (called X and Y for ease, see figure below for structure), can be incorporated into natural DNA strands and copied in vitro

Top two images are of unnatural DNA compared with natural C and G bases. Image from Malyshev et al. PNAS 2012.
Top two images are of unnatural DNA compared with natural C and G bases. Image from Malyshev et al. PNAS 2012.

The real problem is getting the synthetic DNA bases inside cells and convincing the cells to incorporate the synthetic molecules into natural DNA.

A group of scientists took a protein from algae that transports nucleotides across cell membranes. They put this protein into E coli. They also put in an extra sequence of DNA that included the synthetic bases X and Y. They then grew the E coli cells in media containing X and Y. The E coli cells were able to take up X and Y from the media via the algal transporter and use it to make copies of the synthetic DNA as the cells replicated and divided.

This means that the natural E coli machinery (DNA polymerases) could copy DNA containing synthetic DNA ‘letters’. Even more amazing is the fact that the synthetic DNA was not removed by DNA repair mechanisms.

This is the first time an organism has been able to copy synthetic DNA.

The next step is to get an organism to produce synthetic DNA. And then to turn the synthetic DNA into synthetic protein. Then we could start to make synthetic organisms. Living robots. Living computers that could produce any protein we like.

The scientists behind this technology founded the startup Synthorx. They have listed a number of potential ways the technology could be used including to make new enzymes and new vaccines.

Read the other posts in the bio-computing series here:

Can biological computers become a reality?

How DNA is made

The Scientific Papers:

Malyshev et al. A semi-synthetic organism with an expanded genetic alphabet. Nature. 2014

Malyshev et al. Efficient and sequence-independent replication of DNA containing a third base pair establishes a functional six-letter genetic alphabet. PNAS. 2012. (free and open access)

Watson and Crick. Molecular structure of nucleic acids: A structure for Deoxyribose Nucleic Acid. Nature. 1953.

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