Researchers make alternatives to DNA and RNA

Called 'XNAs,' they have potential to store and pass on genetic information and could help scientists design better drugs.

By Eryn Brown, Los Angeles Times

April 20, 2012, 4:57 p.m.

DNA and RNA molecules are the basis for all life on Earth, but they don't necessarily have to be the basis for all life everywhere, scientists have shown.

Researchers at the Medical Research Council in Cambridge, England, demonstrated that six synthetic molecules that are similar to — but not exactly like — DNA and RNA have the potential to exhibit "hallmarks of life" such as storing genetic information, passing it along and undergoing evolution. The man-made molecules are called "XNAs."
"DNA and RNA aren't the only answers," said Vitor Pinheiro, the postdoctoral researcher who led the study, which was published this week in the journal Science.

FOR THE RECORD:
Synthetic DNA: An April 21 article in Section A about scientists' studies of synthetic DNA said that viruses used only RNA to store genetic information. In fact, some viruses encode genetic instructions in DNA, like nearly all organisms on Earth. —

Manipulating XNAs to behave like DNA and RNA could help scientists design better drugs, Pinheiro said.

It could also shed light on how life emerged on Earth, and on what living things might look like if they exist beyond our planet.

"Everyone wants to know what aliens would use for DNA," said Steven Benner, a biochemist at the Foundation for Applied Molecular Evolution in Gainesville, Fla., who has synthesized artificial DNA but was not involved in the new study. "Lab experiments tell you about the possibilities in the universe."

In natural life on Earth, the nucleic acids DNA and RNA are formed by sugar molecules — deoxyribose in DNA and ribose in RNA — that link to phosphates to form a backbone onto which the four nucleotide bases attach to form a chain.

Genetic information is stored in the order in which the bases — known by the chemical letters A, C, G and T — are strung along the chain.

DNA forms the template that holds all the information needed to create an organism. RNA takes that information and translates it into proteins, the basic building blocks of biology. (Viruses, which some scientists consider to be a life form, use only RNA.)

To build alternatives to DNA and RNA, scientists often fiddle with one component or another and see how the changes affect genetic function.

Pinheiro and his team worked with six molecules that use different sugars or sugar-like groups in place of deoxyribose and ribose. Something called CeNA, for instance, employs a ring-shaped structure called cyclohexene. Another variant called HNA used a group of atoms called anhydrohexitol.

Collectively, the scientists refer to the group as XNAs. The X stands for "xeno-," the Greek prefix meaning "strange," "foreign" or "alien."

The researchers started with molecules that were already synthesized in other labs or sold by companies. The new part was demonstrating that the molecules were capable of passing along their genetic code. To do this, they had to engineer a group of enzymes that could read information stored in XNAs and write it onto DNA. After making make a bunch of copies of that DNA, they then used the enzymes to write those copies back to XNAs.

The group then showed that HNA was capable of evolution by making lots of copies of it, selecting out the ones with desired characteristics — in this case, the ability to bind to certain proteins — creating more copies of those, selecting out the best ones again, and so on.

"It's domesticated breeding of molecules," said Dr. Gerald Joyce, a researcher at the Scripps Research Institute in La Jolla, Calif., who was not involved in the study.

Joyce, who wrote an editorial for Science about the research, said the techniques Pinheiro and his colleagues used could some day make it easier for scientists to build nucleic acid-based medicines and diagnostic tests.

Today such products rely on RNA or DNA — both of which degrade quickly when exposed to enzymes called nucleases.

"If you take RNA and put it in a dish and breathe heavy, the RNA is a goner," Joyce said.

With an XNA alternative, scientists could produce tests or therapies that are impervious to nucleases, potentially speeding the drug development process, Pinheiro said.

As for XNAs' possible role in the evolution of life, Joyce said that scientists believe life on Earth probably was RNA-based before it became DNA-based — and could have been based on an even simpler XNA, such as TNA (made with a sugar called threose), before that.

"Some molecules developed the ability to replicate their own information, then we were off to the Darwinian races," he said.

eryn.brown@latimes.com