Researchers Create the World’s First Stable Semisynthetic Organism

A team of researchers from The Scripps Research Institute recently created a fully stable semisynthetic organism. The single-celled organism has genetic bases, X and Y, that don’t exist in nature. While the team had previously accomplished this feat, the modified bacteria would lose the synthetic bases as they reproduced. The researchers have now solved this problem with the CRISPR-Cas9 tool. The details are in a paper that was just published in the journal Proceedings of the National Academy of Sciences.

DNA consists of four bases which code for proteins depending on how they’re arranged in the genome. These four bases make up the entire genetic code and are called adenine (A), thymine (T), cytosine (C), and guanine (G). They naturally pair up—adenine pairs with thymine, guanine with cytosine. Scientists have long wondered if this basic code could be rewritten. In 2014, researchers were successful in creating bacteria with two synthetic bases named X and Y. The X and Y bases don’t exist in nature but were incorporated into the genetic code of the bacteria. The organisms were not stable, however, and lost the added bases as they reproduced.

The researchers behind the 2014 study used a genome editing tool called CRISPR-Cas9 to solve the problems that arose with their first set of semisynthetic organisms. The bacteria were losing the added X and Y bases over time as they multiplied. CRISPR-Cas9 is normally used to edit genomes but the research team took advantage of its original function as part of the bacterial immune response. In nature, CRISPR-Cas9 allows a bacterium to take segments of DNA from viruses and other pathogens. These segments are incorporated into the bacterium’s genome, helping the organism “remember” threats. The team edited CRISPR-Cas9 so that the modified bacteria would attack any cells that lacked the X and Y bases. The idea worked and the bacteria retained the bases, even after reproducing.

The use of CRISPR-Cas9 allowed the researchers to create stable semisynthetic organisms—bacteria that contained X and Y bases in addition to the naturally occurring A, T, C, and G bases. Now that scientists know that it’s possible to add synthetic bases to the genetic code, the next step is studying ways to utilize these new bases.


Zhang et al. A semisynthetic organism engineered for the stable expansion of the genetic alphabet. Proceedings of the National Academy of Sciences (2017).

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