Technique Blocks AIDS-Type Viruses
An experimental genetic engineering technique called “antisense” can block infection by the type of viruses that cause leukemia and AIDS, according to Ohio University researchers.
Their results, published today in the Proceedings of the National Academy of Sciences, mark the first time the technique, widely studied in the laboratory, has been shown to work in animals.
Molecular biologist Thomas E. Wagner and his colleagues inserted a special genetic sequence called antisense into the chromosomes of fertilized mouse eggs. When the animals grew up, the antisense molecules produced in their cells made them immune to a virus that causes leukemia in mice.
The same technique could be used to attack the AIDS virus, Wagner said, if researchers can find a way to insert the genetic sequences into human cells.
Molecular biologist W. French Anderson of the National Institutes of Health, who was the first to treat cancer patients with gene therapy, said the Ohio experiment was “very important” because it demonstrated that the antisense gene manipulation can prevent disease.
Mouse leukemia and AIDS are caused by an infective organism called a retrovirus. This is a virus that invades cells, inserts its own gene pattern into the nucleus and forces it to make more virus particles.
“That’s what’s frightening about retroviruses,” Wagner said. “They genetically engineer your chromosomes to make more viruses. Up to now, there’s nothing you can do about it.”
Wagner said his laboratory made a gene that expresses a type of ribonucleic acid, or RNA, that works against the retrovirus. This new gene was inserted into fertilized mouse eggs that were returned to the mother mouse.
When the babies were born, each contained the new gene as part of their chromosomes, and the RNA was produced in white blood cells (lymphocytes), the normal target of the virus.
“All of the lymphocytes are making this little piece of RNA,” Wagner said. “It doesn’t do anything but hang around in the cell unless it’s infected by a retrovirus.”
When the cells were invaded, the antisense molecules used in the experiment specifically masked the genetic codes that a retrovirus needs to package new viral particles so they can spread infection. Without the proper packaging, the viral particles produced were not infectious and thus were “shooting blanks,” Wagner said.
Result: The virus infection is stopped.
Wagner said that to test the system, the researchers injected leukemia virus into mice carrying the antisense gene and into mice with normal genes.
Eleven of 36 mice with normal genes developed leukemia, but none of the transgenic mice developed symptoms of leukemia.
Wagner said this is the first time the theory of antisense has been demonstrated by preventing disease.
