Monday, March 10, 2008

Artificial Letters Added to Life’s Alphabet

Two artificial DNA ‘bases’ that can be actively replicated by natural enzymes have been created by US researchers. The addition of two extra bases to the existing 4 bases (cytosine, guanine, adenine, and thymine) will create greater genetic diversity.

Researches hope to in future implement these new bases into the genetic code of living organisms.

These unnatural but functional new base pairs are the fruits of nearly a decades worth of research by chemical biologist Floyd Romesberg, at the Scripps Research Institute, La Jolla, California, USA.

Rosenberg and his colleagues painstakingly created nearly 200 potential new genetic bases each with slight variations on the original bases. Unfortunately these potential bases all failed as their structure and chemistry were not similar enough to the real thing and the polymerase enzymes (the enzymes that replicate DNA inside cells) could not copy them properly.

Frustrated by the slow pace designing and synthesising potential new bases one at a time, Romesberg turned to large scale experiments generating many potential bases at random, which were then screened to see if they would be treated normally by a polymerase enzyme similar to drug development.
With the help of graduate student Aaron Leconte, the group synthesized and screened 3600 candidates. Two different screening approaches turned up the same pair of molecules, called dSICS and dMMO2.

But the team still faced a challenge. The dSICS base paired with itself more readily than with its intended partner, so the group made minor chemical tweaks until the new compounds behaved properly.

Romesberg notes that DNA and RNA are now being used for hundreds of purposes: for example, to build complex shapes, build complex nanostructures, silence disease genes, or even perform calculations. A new, unnatural, base pair could multiply and diversify these applications.

For more info go to
Journal of the American Chemical Society

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