Genetic approach shows bright promise against AIDS

Laura S. Marshall, laura.marshall@photonics.com

The immunological battle against AIDS could someday be won in our genes – with a little help from a few glow-in-the-dark cats.

A new genome-based immunization strategy from the Mayo Clinic in Rochester, Minn., could help fight feline AIDS and even illuminate ways to combat human diseases, including HIV/AIDS, which has killed more than 30 million people. There is no effective vaccine on the horizon.

Each year, millions of cats suffer and die from feline immunodeficiency virus (FIV), which causes AIDS in cats the same way HIV does in people: by depleting the body’s infection-fighting T cells. Naturally produced protective proteins called restriction factors are ineffective against FIV in cats and HIV in humans.

A genome-based immunization technique could shed light on ways to fight feline immunodeficiency virus and even HIV/AIDS, among other diseases. A jellyfish gene included for tracking purposes makes the offspring cats glow green. Courtesy of Mayo Clinic.

The interdisciplinary research team looked to jump-start evolution by creating cats with an inborn immunity to the virus. Normally, over vast spans of time, restriction factors evolve to defend mammals against virus invasion, but the Mayo physicians, virologists, veterinarians and gene therapy researchers, working with scientists in Japan, didn’t want to wait that long.

They devised a way to insert a rhesus monkey restriction factor – known to block FIV infection in a culture dish – into the cat genome, creating cats that produce the proteins on their own and even pass the genes on to their kittens. A jellyfish gene, added for tracking purposes, has the side effect of making the offspring cats glow green.

The technique, called gamete-targeted lentiviral transgenesis, involves inserting genes into feline eggs before they are fertilized. This is the first time it has been successful in a carnivore. The method is highly efficient, so that nearly all offspring have the genes, and the defense proteins are made throughout each cat’s body. The findings appeared online in Nature Methods.

This specific genome modification approach will not be used directly to treat people with HIV or cats with FIV, but it will help medical and veterinary researchers understand how restriction factors can advance gene therapy for AIDS in both humans and cats.

“One of the best things about this biomedical research is that it is aimed at benefiting both human and feline health,” said Dr. Eric Poeschla, a molecular biologist at the Mayo Clinic and leader of the study. “It can help cats as much as people.”