TWO artificial DNA “letters” can link up just like the natural versions, paving the way for incorporating the newcomers into living cells.

Synthetic biologists are racing to come up with artificial versions of the building blocks of life. “We have been basically reinventing the genetic alphabet from the bottom up,” says Steven Benner of the Foundation for Applied Molecular Evolution in Alachua, Florida. Hopes for such fake DNA range from developing new drugs to creating artificial life.

In 2006, Benner and his colleagues built two bases, dubbed Z and P, which bond together to form a pair (ZP) in a similar way to the two natural DNA base pairs – AT and GC.

Shortly after, in 2008, a group led by Floyd Romesberg at the Scripps Research Institute in La Jolla, California, built two more bases and showed that, just like DNA, natural enzymes could be used to replicate them. But their artificial base pairs were linked together into longer strands of DNA in a different way.


“What we know about normal DNA is you have runs of the same base, AAAA or TTTT,” says Millie Georgiadis of Indiana University in Indianapolis. Because of the way they are joined together Romesberg’s bases can’t form such long runs.

Now Georgiadis and Benner have shown that their Z and P bases can form these runs, behaving just like natural DNA. Using X-ray crystallography they found that the bases could incorporate themselves into strands of both natural and unnatural bases that included runs of Z and P up to six bases long.

The researchers also showed that the strands took on the same two forms that normal DNA uses inside cells: the familiar helical structure, called the “B” form, and a wider “A” form that DNA adopts when it is binding with a protein (Journal of the American Chemical Society, doi.org/4r9).

“DNA normally has to adopt different forms to interact with different sets of proteins,” Georgiadis says. “The fact that Z and P can adopt these forms suggests that [DNA made with these bases] will behave in a cell like natural DNA.” She says the ultimate goal is to “create new things”.

The fact that Z and P can adopt two forms suggests they will behave like natural DNA

The work is impressive, says Romesberg. The ZP pair “can really function like a GC or an AT”, he says.

This article appeared in print under the headline “Artificial DNA links up just like the real thing”