May 8, 2014 - The first report of a bacterium whose genome contains man-made DNA
building blocks opens the door for tailor-made organisms that could be used to produce new drugs and other products.
All living creatures have a DNA
"alphabet" of just four letters, which encode instructions for the proteins that perform most of the key jobs inside cells. But expanding that alphabet to include artificial letters could give organisms the ability to produce new proteins never seen before in nature.
The man-made DNA
could be used for everything from the manufacture of new drugs and vaccines to forensics, researchers say.
"What we have done is successfully store increased information in the DNA
of a living cell," study leader Floyd Romesberg, a chemical biologist at The Scripps Research Institute
in La Jolla, California, told Live Science. Yet many steps remain before Romesberg and his colleagues can get cells
to produce artificial proteins.
The field of synthetic biology involves tinkering with DNA
to create organisms capable of novel functions in medicine, energy and other areas.
alphabet consists of four letters, or bases: adenine, thymine, guanine and cytosine (A, T, G and C). Adenine pairs with thymine, and guanine pairs with cytosine. RNA
is a genetic material similar to DNA, except it has a different chemical backbone and replaces the base thymine with uracil (U).
Living things translate DNA
into proteins through a series of steps. First, enzymes "transcribe" the DNA
into RNA. Then, structures called ribosomes translate the DNA
into proteins, which are made up of strands of molecules called amino acids.
Ultimately, the researchers aim to create organisms that can produce artificial proteins. But first, they need to show that the DNA
containing the man-made letters can be transcribed into RNA, and that this RNA
can be translated into proteins.
In the study, Romesberg and his team created an new pair of DNA
letters not found in nature and inserted the pair into cells of Escherichia coli
bacteria. Getting the DNA
into the cells is not easy, but the researchers were able to do it by way of a transporter, a protein that moves materials across cell membranes.
Inside the cells, the man-made DNA
got spliced into a plasmid, a circular piece of DNA
found in bacteria. The plasmids replicated, without rejecting the foreign DNA
or affecting the cells' growth, the researchers reported.
Now that the scientists have demonstrated an organism can incorporate artificial DNA
letters into its genome, the next step will be showing it can convert the DNA
into new proteins, which could be used to produce better drugs.
Researchers expanded the genetic alphabet from four letters, or bases, to six, vastly increasing the number of proteins that can be made. Proteins
have become an important new type of drug, because cells can do the work of making them and because molecular biology techniques can be used to help proteins "evolve" to have desired properties, Romesberg said. But proteins are limited to only 20 building blocks, known as amino acids.
"Compare this to a medicinal chemist, who explores a much greater diversity of structures in the small-molecule drugs they synthesize," Romesberg said. "We hope to be able to combine the best of both small-molecule and protein drugs."
The research paves the way for "designer" organisms with custom-made genomes that are capable of performing useful tasks, like making drugs. Already, researchers have created the first "synthetic organisms" - artificial bacteria and yeast - which have man-made DNA
sequences in their genomes.
The researchers are now working on expanding the DNA
alphabet of yeast cells, and eventually hope to do the same for mammalian cells, which have properties that make them better at producing protein drugs. Expanding the genetic alphabet of an entire multicellular organism such as a human wouldn't be possible with the current technique, however, because the artificial letters must be directly inserted into each cell, Romesberg said.