Scientists create artificial DNA molecule

Scientists have successfully created a pair of DNA nucleobases, which, like adenine, guanine, cytosine, and thymine in natural DNA, can copy themselves nearly as well as the real thing.

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With their X-ray crystallography images, Romesberg — along with colleagues in nearby San Diego, Calif., and in Germany — found that while NaM and 5SICS aren't lined up edge-to-edge inside a strand of DNA, they shift so they are in the correct formation for copying when DNA polymerase comes along. "The DNA polymerase apparently induces this unnatural base pair to form a structure that's virtually indistinguishable from that of a natural base pair," said Denis Malyshev, another Scripps Institute chemist in the study. He and his colleagues think that the chemical bonds the artificial bases use are flexible, so they can shift positions easily.

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They also found that when the artificial bases slide inside the polymerase, like a sheet of paper placed inside a copying machine, the polymerase undergoes the same chemical interactions as it does when it works with natural bases. They also found the polymerase refuses to pair an artificial base with a natural base, which is similar to how polymerases will only match A's to T's and C's to G's.

In the future, artificial DNA building blocks like NaM and 5SICS could expand the well-known "A, C, G, T" vocabulary of DNA, according to a statement from the Scripps Institute. Synthetic bases may work even if they aren't shaped like natural bases, as long as they have flexible chemical bonds, the way NaM and 5SICS do.

Romesberg, Malyshev and their colleagues are now working on tweaking NaM and 5SICS so that natural DNA strands with those synthetic bases added will copy even more efficiently, at a rate that's closer to the rate found in all-natural DNA, they wrote in their paper. Once they accomplish that, they can start building synthetic organisms from the ground up. "If we can get this new base pair to replicate with high efficiency and fidelity in vivo [i.e., in a living organism], we'll have a semi-synthetic organism," Romesberg said.