Scientists have created the first organism with synthetic DNA that can replicate in a cell, an achievement that promises to add new letters to the genetic code underlying life on Earth.
In the natural world, just two chemical base pairs, known simply as A-T and C-G, constitute the building blocks of DNA in all life forms. Research published Wednesday in the journal Nature describes the creation of a cell that contains a man-made base pair, dubbed d5SICS-dNAM.
By expanding the natural boundaries of what constitutes life, scientists hope they can one day create new proteins that can handle a variety of chores in the body, potentially leading to unique ways to attack disease. The approach is safe, the researchers said, because it includes a chemical additive that the cell needs to survive.
“We created an organism that lives and stably harbors genetic information in its DNA,” said Floyd Romesberg, a chemist at the La Jolla, Calif.-based Scripps Research Institute, whose laboratory created the new organism. “Instead of two base pairs, it has a third.”
All life on Earth is based on the combination of four chemicals. Adenine bonds naturally with thymine to create the A-T section of the formula, while guanine and cytosine make up the C-G part. The joining of these base pairs in different combinations creates amino acids and proteins that power life.
Romesberg’s work differs from other research in the field of genetic engineering in that it involves creation of components that are purely synthetic and are “integrated into the machinery of life in a cell,” he said in a telephone interview.
Other scientists in the field, notably J. Craig Venter, work by constructing genetic material from natural building blocks, or natural components of DNA and proteins.
Starting in 2009, Romesberg and his laboratory created about 300 nucleotides with the newly constituted DNA before landing on ones they believed might be able to replicate in a cell. They then used a special chemical transporter to get the synthetic base pair into an E. coli cell, where it replicated without affecting cell growth. That suggests it was not recognized as atypical by the body’s natural DNA repair machinery, according to the paper.
Eventually, the goal is to see whether the synthetic bases can be made to produce proteins, a feat Romesberg predicts may happen in just two years.
“From a practical perspective, we are interested in exploring the potential of expanding the evolution of proteins to include proteins with unnatural amino acids,” Romesberg said.
One potential application may be the ability to combine protein-based medications that are the hallmark of biotech with traditional small-molecule drugs.
“We have now given the genetic alphabet a new letter,” Romesberg said.