Rethinking Healthcare

XNA: synthetic DNA capable of heredity and evolution

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By changing the sugars in DNA and RNA strands, scientists created 6 new kinds of genetic molecules called XNAs. These variants can help scientists design better drugs and diagnostic tests.

The new man-made molecules are called XNAs, and they’re uncannily similar to the genetic instructions for life found in every living thing on earth.

These strands of synthetic polymers can store, copy, and pass on genetic information the way DNA does. And they can even be evolved in the laboratory.

By baring these hallmarks of life, the lab-made variants could help researchers develop better drugs and therapeutic nanotechnologies.

DNA (pictured) and RNA consist of 4 nucleic acid bases – the chemical letters A, G, C, and T – that run along a backbone of phosphates and sugars. DNA uses deoxyribose sugars, while RNA uses ribose.

With XNA, those sugars are replaced by a different sugar – one of 6 alternatives, including hexitol, threose, and arabinose. The 6 resulting molecules are known as xeno-nucleic acids ("xeno" is Greek for "foreign").

Scientists have previously developed XNAs, but it’s difficult to make them in large quantities. Until now, they haven’t figured out a way to copy what they’ve made.

This team of researchers, led by Philipp Holliger at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK, engineered enzymes that can synthesize XNA from a DNA template, and others that can turn XNA back into DNA.

They can do this with 95% accuracy – confirming that replication, heredity, and evolution are possible in these alternative backbones. Nature explains:

Faithful genetic transmission over successive DNA-to-XNA cycles allowed researchers to select for only those XNAs that attached to certain target proteins from a pool of random samples – a process akin to evolution over multiple generations.

It's the domesticated breeding of molecules.

And its uses for medicine?

  • Doctors already prescribe biological products such as enzymes and antibodies to treat certain diseases, but these drugs break down quickly in the stomach and the blood stream. Because XNAs are somewhat foreign, Popular Mechanics explains, they’re not broken down as quickly in the body, as it hasn’t evolved enzymes to digest them.
  • Today’s nucleic acid-based medicines and diagnostic tests rely on RNA or DNA, both of which degrade quickly when exposed to enzymes called nucleases. An XNA alternative could be impervious to those enzymes, potentially speeding the drug development process, Los Angeles Times reports.
  • Their ability to slip from the bloodstream into diseased cells means that XNA-based drugs “might have a future to rival antibodies,” Holliger tells Bloomberg.
  • According to Nature, replicable, evolvable XNAs could help the development of artificial genetic polymers that can bind and inhibit proteins, such as those involved in macular degeneration, for example.

The work was published in Science last week.

Image of DNA via Wikimedia

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Janet Fang

Contributing Editor

Janet Fang has written for Nature, Discover and the Point Reyes Light. She is currently a lab technician at Lamont-Doherty Earth Observatory. She holds degrees from the University of California, Berkeley and Columbia University. She is based in New York. Follow her on Twitter. Disclosure