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Artificial DNA Can Replicate in Lab, Researchers Find

Scientists moved a step closer to synthesizing new life forms in the laboratory after researchers showed that artificial genetic material called XNA can be replicated in the test tube much like real DNA.

Researchers at the Medical Research Council Laboratory of Molecular Biology in the U.K. demonstrated for the first time a way to extract information from the artificial genetic molecules and mass produce copies of them. The finding, published today in the journal Science, shows that DNA and its sister molecule RNA may not be the only chemical structures upon which a living unit can be based.

“Life is based on this amazing ability of DNA and RNA to store and propagate information,” said Philipp Holliger, a Medical Research Council molecular biologist and senior author on the study. “We have shown that the basic functions of DNA and RNA can be recapitulated” with new artificial molecules.

The scientists invented a lab method for making copies of synthetic DNA. They also developed a way to make XNA fragments that evolve with desired properties. In particular, they created XNA fragments that could bind with great specificity to a molecular target in the HIV virus. The discovery could create a new platform for devising targeted drugs to treat a variety of diseases, researchers said.

“This brings us one big step closer to artificial life,” said Gerald Joyce, a biochemist at Scripps Research Institute in San Diego, in a telephone interview. “The heart of what life is, is the replication of genetic information,” he said. Joyce wrote a commentary accompanying the study.

Hereditary Molecule

DNA, deoxyribonucleic acid, is the hereditary molecule at the center of our cells. It contains code, in the form of chemical letters A, T, C and G, that tells the body how to make proteins that perform numerous bodily functions such as regulating blood sugar or fighting infections.

XNAs, or xeno-nucleic acids, maintain the same four-letter chemical code while altering the backbone of the DNA “double helix” molecule to add properties such as acid resistance.

While XNAs aren’t new, chemists have always had to make them one at a time, limiting their utility, Joyce said. With the new work, “if I give you a few XNAs in the morning, I can come back in the afternoon and you can give me trillions of copies.”

The work may give scientists a new method for creating designer drugs and diagnostic tools. “There are a whole host of opportunities in biotechnology which now become possible,” Holliger said.

While researchers have been working for years on therapies based on DNA and RNA, a limitation is that the nucleic acids break down easily in the body, and need to be modified to make them more stable, said Joyce.

“If you put a sample of RNA on a sterile dish and just breathe on it, it is a goner,” said Joyce.

DNA Still Needed

One limitation of the new method is that it isn’t entirely artificial, and natural DNA is still required as an intermediate step in the XNA copying process.

The XNA work provides a new way of developing designer nucleic acid drugs that could resist breakdown, or have other desirable properties, such as the ability to slip from the bloodstream into diseased cells, said Holliger.

XNA-based drugs “might have a future to rival antibodies,” he said. Antibody drugs, such as Roche Holding AG’s Avastin for cancer and Abbott Laboratories’ Humira for autoimmune diseases, have become some of the biggest selling therapies in recent years.

The research “is a tour-de-force” that could have “direct therapeutic impact,” said Andrew Ellington, the Fraser Professor of Biochemistry at the Center for Systems and Synthetic Biology at the University of Texas in Austin, in an e-mail.

Interfering RNAs

It also could help drug researchers working on so-called small interfering RNAs, he said. Companies working on such drugs include Alnylam Pharmaceuticals Inc. in Cambridge, Massachusetts. RNA is a similar molecule to DNA that transports genetic information from the cell nucleus to the molecular factories where proteins are made.

Still, “the ultimate impact of the work won’t really be known until folks have had a chance to try out the cornucopia of diversity” the researchers have provided, Ellington said.

The Medical Research Council has applied for patents on the new XNA method, Holliger said. Researchers from Arizona State University, University of Southern Denmark, and the Rega Institute for Medical Research in Belgium were also involved in the study.

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