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Helicos’s RNA mapping called a step forward

Cambridge firm’s method could help control diseases

By Elizabeth Lopatto
Bloomberg News / September 24, 2009

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NEW YORK - Scientists at Cambridge-based from Helicos BioScience Corp. have mapped RNA, or ribonucleic acid - a key player in each person’s genetic blueprint - in a step that might boost researchers’ search for the roots of disease.

The technique for showing the sequence of RNA is more accurate than a previous method, which required the RNA sample to be converted to its cousin DNA before it could be measured, according to a report in the journal Nature yesterday.

The technology will be commercially available as soon as next year and could benefit companies building new RNA-based drugs.

Being able to identify RNA directly will uncover corresponding areas of DNA, previously called “junk,’’ that has turned out to have valuable information, said Patrice Milos, the study’s head researcher.

Many genetic markers of disease discovered in the past several years have been in the “junk’’ sections, said Milos, the chief scientific officer at Helicos.

“Often, the particular genetic markers associated with common diseases lie outside the coding regions of genes,’’ Milos said. RNA is active in these regions, so it could tell researchers what the gene segment’s purpose is.

RNA is a single-stranded molecule that helps translate genetic information from DNA into proteins that carry out DNA instructions. Researchers have found that RNA can block proteins from being made, a process called RNA interference.

Companies such as Alnylam Pharmaceuticals Inc., also of Cambridge, and RXi Pharmaceuticals Corp., of Worcester, are attempting to exploit RNA interference for therapies in order to block actions of genes.

Viruses are composed almost entirely of genetic material; cancer is principally a disease of flawed DNA. Turning off certain genes might halt the biological machinery that drives illnesses as varied as bird flu and AIDS.

The new RNA sequencing technology will be available sometime next year, Milos said. It will be compatible with the HeliScope single-molecule sequencing machine, which costs $999,000, Milos said. The individual channels for RNA analysis will cost $300 each. The HeliScope has two flow cells, each of which allows for 50 channels. A full analysis would be about $300 times 50, or $15,000, Milos said.

Direct mapping of RNA will be used more often if it demonstrates it is better than previous methods, if it is relatively simple, and if it does not cost too much, said George Church, a Harvard University scientist whose findings helped spur the US human genome project in the 1980s.

“The competition is a moving target, but for now, Helicos is a clear leader on all three,’’ Church said in an e-mail. He was not involved in yesterday’s research report.

Researchers are already moving away from using DNA micro-arrays, a way of examining DNA, to newer ways to sequence gene molecules, Church said. “This will drive that trend even further,’’ he said.

Previously, to sequence RNA, researchers created so-called complementary DNA through a chemical reaction. When the Helicos researchers compared the direct sequencing of RNA to the complementary DNA method, they found that 4 to 5 percent of the molecules measured in the DNA method were created in the conversion process. Direct sequencing, on the other hand, detected exactly what had been put in the test tube, Milos said.

“There really were some biases that were created through complementary DNA,’’ Milos said.