15WWW.CEN-ONLINE.ORG JULY 20, 2009

WHEN THE HUMAN GENOME stutters by re-peating sequences of three nucleotides, dis-ease often follows. Researchers are now pro-

posing to treat one such disease—a form of muscular dystrophy—by delivering complementary nucleotides that silence the stuttered sequences.

Affecting one in 8,000 people, myotonic dystrophy type 1 (DM1), is the most common form of adult-onset muscular dystrophy. DM1 causes muscle cells in the face, hands, and legs of adults to waste away. In many cases the disease also triggers an irregular heartbeat. But unlike Huntington’s disease, which is caused by a toxic protein made from RNA that contains repeated stretches of three nucleotides, DM1 is caused by toxic RNA containing the stuttered sequences. In fact, the stretch of cytosine-uridine-guanine repeats is located in a part of the RNA that is normally not translated into a protein.

The troublesome, repetitive RNA forms a hairpin structure in the nucleus. This hairpin structure is irresistibly at-tractive to a protein called MBNL1, many molecules of which bind the RNA to form toxic aggregates. The binding of mol-ecules of MBNL1 to the hairpin also pre-vents the RNA from being exported to the cytosol and translated into an important protein kinase.

With this in mind, Thurman M. Wheeler, Charles A. Thornton, and their colleagues at the University of Rochester came up with the idea to distract the toxic, repeated sections of RNA by means of a complementary sequence of so-called morpholino an-tisense nucleotides ( Science 2009, 325, 336).

When they inserted the antisense sequence into mice with the muscular dystrophy, the therapeutic sequence of nucleotides blocked the harmful coupling of MBNL1 and the triplet sequence RNA and reduced many of the symptoms of DM1.

The work is “a highly significant advance,” com-ments Stephen Tapscott, a biologist who studies the disease at the University of Washington School of Medicine. But he points out that like many oligonucle-otide treatments, getting the remedy into the nucleus is a serious stumbling block. —SARAH EVERTS

A FTER YEARS of mostly sitting on the sidelines in the alternative energy game, ExxonMobil is joining in a big way. The oil and gas giant will in-

vest as much as $600 million to develop algae-derived biofuels with California-based Synthetic Genomics Inc.

For Exxon and SGI, the goal is to genetically engi-neer photosynthetic algae to produce a hydrocarbon that can be processed in existing oil refineries and turned into fuels that work in existing cars.

If all goes as planned, Exxon will fund $300 million or more in R&D at SGI over five or six years. At the same time, Exxon plans to spend $300 million on re-search at its own labs in Clinton, N.J., and Fairfax, Va. Commercializing algae-based biofuels will cost billions of dollars more, the company says.

SGI was founded in 2005 by J. Craig Venter, one of the pioneers of human genome sequencing. Its early focus was on rewiring microorganisms to produce hy-drogen and ethanol.

Exxon has long questioned the viability of corn-based ethanol as a transportation fuel. Emil Jacobs, vice president of R&D at ExxonMobil Research & En-

gineering, told reporters last week that the algae effort comes out of a high-powered company task force on alternative energy. After the task force explored the landscape for two years, “biofuels from algae rose to the top,” he said.

SGI likewise stood out as a potential partner for Exxon because of its success in engineering algae to continuously secrete hydrocarbons. According to Ven-ter, SGI’s competitors rely on growing algae and peri-odically harvesting them for the oil they contain. With further development, the partners say, their algae could yield more than 2,000 gal of fuel per acre per year, ver-sus just 250 gal for corn-based biofuels.

The agreement between Exxon and SGI gives cred-ibility to algal biofuels, a field that “has had more than its share of fly-by-night promoters,” says David Wood-burn, a green technology analyst at the investment advisory firm ThinkEquity.

Although Woodburn agrees that algae have high potential, he points out that Exxon and SGI haven’t decided on basics such as the specific organism they will use and whether they will grow it in open ponds or closed bioreactors. “They are going back to basic build-ing blocks,” he says. —MICHAEL MCCOY

RNA DISTRACTION IS THERAPEUTIC

MEDICINE: Antisense nucleotides could one day combat a form

of muscular dystrophy

EXXON INVESTS IN ALGAL BIOFUELS ALTERNATIVE ENERGY: Project

represents a new direction for oil giant Algal plates in Synthetic Genomics Inc.’s La Jolla, Calif., labs.

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Toxic RNA (red) forms aggregates in the nucleus (blue) of muscle cells (green). Image is magnified 1,000 times.

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