Scientists 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 research, 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.
Vitor Pinheiro and colleagues from Philipp's group used sophisticated protein engineering techniques to adapt enzymes, that in nature synthesise and replicate DNA, to establish six new genetic systems based on synthetic nucleic acids. These have the same bases as DNA but the ribose linkage between them is replaced by quite different structures.
In doing this they showed that there is no functional imperative limiting genetic information storage to RNA and DNA. Therefore, the discovery has implications for the understanding of life on Earth. As other informational molecules can be robustly synthesised and replicated, the emergence of life on Earth is likely to reflect the abundance of RNA (and DNA) precursors in early Earth.
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.
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. In particular, they created XNA fragments that could bind with great specificity to a molecular target in the HIV virus.
XNA-based drugs “might have a future to rival antibodies,” he said. Antibody drugs, such as Roche Holding AG (ROG)’s Avastin for cancer and Abbott Laboratories’ (ABT) Humira for autoimmune diseases, have become some of the biggest selling therapies in recent years.
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.
For medical use, the development of functional nucleic acids, called aptamers, with diagnostic, therapeutic and analytical applications. Aptamers can have a number of significant advantages over the current small molecule and antibody-based therapies. For example, they bind their target molecule with high specificity (like antibodies) but being smaller they are expected to have better tissue penetration. They have low-toxicity and low-immunogenicity and they can be chemically modified to improve their stability and pharmacokinetic properties.
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.
“It’s a breakthrough,” said Gerald Joyce of The Scripps Research Institute in La Jolla, California, who was not involved in the study—“a beautiful paper in the realm of synthetic biology.”
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.
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.
It also could help drug researchers working on so-called small interfering RNAs, he said. Companies working on such drugs include Alnylam Pharmaceuticals Inc. (ALNY) 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.
In the field of synthetic biology, this represents a breakthrough, and might change our understanding of life itself. The implications of the study will likely prove to be vast for a multitude of fields of study.
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