It’s DNA Jim, but not as we know it

Artificial DNA variant could aid medicine, biotechnology and nanotechnology

If aliens have DNA, it might look something like this.

Chemists have synthesized a DNA-like molecule using unnatural versions of the A, T, C and G “letters” that make up the genetic code. The resulting molecule has greater structural stability than natural DNA and would resist breakdown by DNA-degrading enzymes in cells, the team reports in the July 23 Journal of the American Chemical Society.

“The artificial DNA may be a superior building scaffold for constructing medical and nanotechnological structures,” says lead scientist Masahiko Inouye of the University of Toyama in Japan. “Our research opens the door to … creating DNA-like molecules similar to natural DNA in terms of their ability for potential information storage.”

While other variants of DNA and its cousin RNA have been made before, the new molecule is the first to have unnatural versions of the compounds that constitute all four letters of the genetic code, Inouye and his colleagues report.

The variant is also the first to replace the bond holding each letter to the helix-shaped “backbone” with a more rigid triple bond. This new bond is what gives the unnatural DNA its greater stability and resistance to enzymes.

Like natural DNA, the new molecule can form a triple helix as well as a double helix. Preliminary tests show that the DNA-like variant has some ability to pair up with natural DNA to form a hybrid double helix, but this work is still ongoing, Inouye says.

“The DNA structure is a whole lot more pliable than we originally thought, and that’s fascinating,” comments Floyd Romesberg, a molecular biologist at the Scripps Research Institute in La Jolla, Calif. “This is coming along with a [chemical] structure that’s been preserved for millennia and saying, ‘Well, I’m bored. I want to try a different architecture.’”

Nanotechnology researchers have eyed DNA as a possible building block for assembling structures at the nanoscale. Strings of DNA bind to each other in predictable ways determined by genetic code, which makes them attractive as an engineering material. The ability to customize DNA’s structural and binding traits will give nanotechnologists even more control, Romesberg says. Scientists are also developing novel drugs that use snippets of DNA or RNA to treat diseases. Enzymes in the body rapidly degrade regular RNA, comments Martin Egli, a structural biologist specializing in nucleic acids at VanderbiltUniversity in Nashville, Tenn. Egli says the chemical modifications made by Inouye’s group should be easy to apply to RNA as well.

“It’s kind of hard to imagine that there will ever be a [DNA- or RNA-] based drug that will not be chemically modified,” Egli says.

Inouye says the next step is to look more closely at how well the new molecule binds to natural DNA and RNA, important for potential medical uses.

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