We can build it better: The First Semi-Synthetic Organism

DNA typewriter

Not anymore…

Normally I do one post a day, but I could NOT wait to share this. Scientists at The Scripps Research Institute (TSRI) have engineered a bacterium whose genetic material includes an added pair of DNA “letters,”  not found in nature. The cells of this new bacterium can even replicate the unnatural DNA bases more or less normally, for as long as the molecular building blocks are supplied to the bacterium.

I don’t even really know where to start with this, so let’s start with the basics, normally in nature, everything, everywhere [that we know of] has four different letters in it’s DNA, A-T, G-C, that is is and they only go together in that order A with T and G with C, never will you see a T with a G for example.

That is it, just 4 DNA “letters” which write everything on the planet from the smallest virus to the largest animals. But now, now we have a synthetic third pair [or 6 "letters"] to work with.

“Life on Earth in all its diversity is encoded by only two pairs of DNA bases, A-T and C-G, and what we’ve made is an organism that stably contains those two plus a third, unnatural pair of bases,” said TSRI Associate Professor Floyd E. Romesberg, who led the research team. “This shows that other solutions to storing information are possible and, of course, takes us closer to an expanded-DNA biology that will have many exciting applications — from new medicines to new kinds of nanotechnology.”

The reason this is so exciting [not only because it is cool] is because this could lead to a whole slew of new medical advancements, everything we know could be changed, especially if we can learn the language of the DNA. This would be equivalent to when the number 0 was first invented [okay technically it is a place holder], this is big.

The technical aspect of this is mind blowing, when you combine A-T or G-C together in strands they are equal “length” like a zipper, it all fits together and forms a nice even package. And like a zipper, the binds that tie A to T or G to C take about as much, let’s say force, to “unzip”, they also had to be copyable when the DNA was replicated.

This was no easy task but, in 2008 they found just that new base pair — a natural base pair would be A-T or G-C — but that was only half the battle, the bigger challenge was placing this new base pair into the DNA of something complex, like a living cell.

In the new study, they finally managed to do it. Published in Nature, it explains the technical aspects of how they overcame everything.

The scientists created a circular piece of DNA [called a plasmid] and  inserted it into cells of the common bacterium E. coli. The plasmid DNA contained natural T-A and C-G base pairs along with the best-performing unnatural base pair Romesberg’s laboratory had discovered, known as d5SICS and dNaM. The main goal was to get the E. coli cells to replicate this semi-synthetic DNA as normally as possible.

Have no fear, we will not see any mutant E. coli anytime soon. Even when they inserted this new base pair they still had to figure out how to get the building blocks into the cell, they did this by finding a triphosphate transporter, made by a species of microalgae, that was good enough at importing the unnatural triphosphates.

“That was a big breakthrough for us — an enabling breakthrough,” said Malyshev.

What is even cooler is that when the triphosphate base pair was removed from the medium that the E. Coli lived in, –meaning they could not get any more of the “building blocks” for the unnatural base pair– the E. Coli was still able to replicate and eliminate the new base pair. In other words, it reverted back to an organism with A-T and G-C like any other organism in the world.

This shows that they have control of the system. That is important if they are to provide any sort of gene therapy in the future for example.

 “In principle, we could encode new proteins made from new, unnatural amino acids — which would give us greater power than ever to tailor protein therapeutics and diagnostics and laboratory reagents to have desired functions,” Romesberg said. “Other applications, such as nanomaterials, are also possible.”

I cannot wait to see what types of new and interesting technology that will come out of this.

Already know your RNA from your DNA, you probably want the full study, which you can find — here!

Sources:
Malyshev D. (2014). A semi-synthetic organism with an expanded genetic alphabet, Nature, DOI:

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