New gene technique for transgenic animals

Jan. 10, 2002 at 1:05 PM
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PASADENA, Calif., Jan. 10 (UPI) -- A new gene delivery technique using a modified HIV virus will soon make it easier to create transgenic animals -- which contain genes of other species -- for research and industrial applications.

Scientists say this advance, reported for the first time in the journal Science, promises to make genetic research cheaper and more efficient, particularly in the area of disease.

"The ability to manipulate species other than mice through this new method is very exciting in particular," said senior researcher David Baltimore, president of the California Institute of Technology in Pasadena. "A number of people are adopting the technique already."

Transgenic animals contain genes from other species and are vital to biomedical research. Gene delivery methods usually target the earliest stages of embryonic development, when organisms are most malleable. Most techniques still are quite costly, relatively inefficient, technically demanding and unworkable in most animal species.

Scientists have attempted to use retroviruses such as HIV, the virus responsible for AIDS, as gene delivery vehicles for decades. Retroviruses copy their genetic material directly into host chromosomes easily, theoretically allowing scientists to avoid the complex surgical techniques other gene transfer methods require.

However, the creation of transgenic animals through retroviruses has proven impractical up to now. Previously, the germs appeared "silenced" or inactivated as the transgenic embryo developed, leading to nearly undetectable levels of expression of the transferred gene.

"This new technique solves a quarter-century puzzle of scientists who have tried to use retroviruses as vectors for gene transfer. It has never worked before," explained biologist Rudolf Jaenisch of the Whitehead Institute in Cambridge, Mass., one of the founders of transgenic science.

The researchers in California used components from HIV as the delivery mechanism in their experiments. HIV is a lentivirus, a type of retrovirus biochemically more complex than its brethren.

"All the guts are taken out of the HIV -- it's not something that can cause disease," Baltimore said in an interview with United Press International.

Baltimore's team outfitted the retroviral vector with a green fluorescent jellyfish protein gene and injected it into single-cell mouse embryos on a lab dish. The embryos were then implanted in female mice and carried to term.

The fluorescent gene was expressed in high levels in roughly 80 percent of these mice, some of which had glowing green paws, tails and faces. The gene was transmitted to the mice offspring as well. The researchers also found they could target the gene to specific tissue types -- such as muscle or immune cells -- by coupling the retroviral vector with the appropriate gene sequences.

The scientists believe their delivery mechanism will easily work on other mammals. When the scientists tried the technique on rats -- a species that has so far proven difficult to modify transgenically -- the researchers had a nearly 60 percent success rate.

"This even opens up the possibility of transgenic primates," Jaenisch commented. "There are a lot of potential applications from these findings."

Baltimore suggested the new method may also work on birds, a class of animals for which no satisfactory method currently exists for creating transgenics.

"Birds are potentially very important for study when it comes to the nervous system," Baltimore told UPI. "Bird song has been very important in research, but no one's ever been able to modify it genetically."

The scientists say their lentiviral approach will probably complement, and not replace, other methods for creating transgenic animals.


(Reported by Charles Choi in New York.)

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