Expanded DNA alphabet wins Science award

Scripps Research professor Floyd Romesberg.

Production of an expanded DNA alphabet in a reproducing life form is the science breakthrough of the year, according to an online vote held by Science magazine.

Scripps Research Institute scientists Floyd Romesberg and Denis Malyshev led a team that inserted two extra DNA letters into E. coli, creating a bacterium with a six-letter DNA alphabet instead of the natural four.

Romesberg's work is the scientific foundation of a new San Diego biotech company, Synthorx.

The modified E. coli faithfully reproduces its genetic code with the two unnatural letters, as long as the synthesized chemicals are included in its food. The unnatural letters pair with each other, creating a third base pair, while natural DNA has only two base pairs.

If the bacterium isn't supplied with the synthesized letters, they are eliminated from its descendants because the modified organism can't synthesize them itself. This is a safety feature to prevent any possible harm if the organism somehow escapes the lab.

The study didn't prove the unnatural letters could be used for any practical purpose; it simply showed that introducing an expanded DNA alphabet into life was possible, something that was widely considered infeasible. Synthorx was formed to find the practical applications.

Malyshev, now a full-time Synthorx scientist, said he is working with the company to develop those practical applications. More basic research continues in Romesberg's laboratory, where Malyshev also works under a collaborative agreement between Synthorx and Scripps.

The expanded alphabet in theory could be used for biological production of a vastly expanded number of proteins than coded for in the natural genetic alphabet. In addition, the DNA itself could be configured into electronic circuits far smaller than those used today, because of the properties of the extra letters, called X and Y.

Romesberg said he is "delighted" with the award.

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Expanded DNA alphabet wins Science award