First gene-altered primate beats the odds

Oregon researchers’ triumph in slipping a bit of another creature’s genome into a monkey has proved that the feat’s possible, but even the bioengineers themselves caution that their technique may not be the best one for future monkey business.

The Oregon Regional Primate Research Center in Beaverton ignited a news frenzy last week with a 3-month-old rhesus monkey’s debut as the world’s first genetically engineered primate.

Named ANDi, a backward homage to ‘inserted DNA,’ the little fellow looks and behaves like his plain-gene playmates. Yet tissue analysis confirms that ANDi carries a jellyfish gene laboriously inserted by scientists, Anthony W.S. Chan, Gerald Schatten, and their colleagues report in the Jan. 14 Science.

The National Institute of Child Health and Human Development in Bethesda, Md., one of the funders of the project, greeted the success enthusiastically. The institute’s interest, explains its director, Duane Alexander, comes from hopes of putting medically important genes into primates to create new models for research on human diseases. Getting a gene into a primate for the first time, regardless of what gene it is, “breaks a technical barrier,” Alexander notes.

To deliver the foreign gene, the ANDi team turned to a crippled retrovirus that can insert DNA without causing infection. Schatten says the group chose the method because, despite drawbacks, it has a good record for incorporating foreign genes into a target’s genome, an advantage in animals less prolific than mice.

To test gene delivery, the researchers selected a gene that gives a jellyfish its glow. The team hitched this green fluorescent protein (GFP) gene to the viral carrier and injected the construct into 224 monkey eggs. They fertilized the eggs with normal sperm and implanted 20 pairs of embryos into surrogate mothers. From the six resulting pregnancies, the team celebrated three healthy births.

Two miscarried fetuses had the GFP gene, and hair shafts and fingernails of one of them glowed green in fluorescent light. Of the live babies, only ANDi seems to carry the gene, but there’s no sign of jellyfish protein in him. And it’s about 4 years too early to tell if he’ll transmit the gene to his offspring.

Mouse-cloning specialist Kevin Eggan of the Whitehead Institute in Cambridge, Mass., says, “It’s exciting that they were able to do this,” but he predicts the next steps may be much harder. Headed by Rudolph Jaenisch, the lab where he works relied on a similar system to create transgenic mice 30 years ago. Modern mouse engineers have turned to other methods because the retrovirus doesn’t handle big genes well and the genes it transfers often get silenced.

Schatten responds that he’s not restricting his research to retroviral vectors. “We fully agree with experts who recognize the limitations,” he says. “This is the first step.”