The elegant structure of DNA has inspired chemists for decades. The simple pairings of the four native nucleobases (adenine, guanine, cytosine, and thymine) produces all of the genetic variations in every known living organism. Based on that basic principle, scientists have made modifications to DNA for a variety of purposes, from creating photonic wires for nanomachines to making completely unnatural DNA for engineered genetics. One aspect of DNA's natural behavior, however, has eluded scientists: DNA replication.
DNA polymerases, which produce copies of DNA molecules, are enzymes that have evolved for millennia, and there has been little success in getting them to work on artificial DNA in living cells. For the development of engineered genetics, it would be advantageous to find ways to hijack a cell’s enzymes for the replication of unnatural DNA. In working towards that goal, Eric Kool and his colleagues from Stanford University and the Massachusetts Institute of Technology managed to insert and replicate artificial DNA in E. coli cells. This first successful example of bypassing the natural cellular replication machinery was published as an advanced article in the Angewandte Chemie International Edition.
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