September 12, 2011

Fluorescent Cats and the Development of Gene-Based Therapies Against HIV

A litter of green-glowing kittens are helping Mayo Clinic researchers develop a gene-based immunization strategy to fight feline AIDS and illuminate ways to combat human HIV infection and other diseases. The goal of the research, published September 11 by Nature Methods, is to create cats with intrinsic immunity to feline immunodeficiency virus (FIV).

Just like HIV in humans, FIV in cats causes AIDS by depleting the body’s infection-fighting CD4 cells. Unfortunately, the feline and human versions of key proteins that potently defend mammals against virus invasion—dubbed restriction factors—are ineffective against FIV and HIV. 

Eric Poeschla, MD, of the Mayo Clinic in Rochester, Minnesota, and his colleagues sought to mimic the way evolution normally gives rise over vast time spans to protective protein versions. They devised a way to insert effective monkey versions of them into the cat genome.

The technique is called gamete-targeted lentiviral transgenesis. Simply put, it involves inserting a gene that activates a monkey restriction factor called TRIMCyp known to block FIV infection into feline eggs before sperm fertilization.

The researchers also injected a jellyfish gene for tracking purposes. This gene, known as green fluorescent protein, made the offspring cats glow; it has been used in several other animal models to track the activity of altered genes.

TRIMCyp blocks FIV by attacking and disabling the virus’s outer shield as it tries to invade a cell. The researchers know that works well in a culture dish and want to determine how it will work in living creatures.

The researchers note that this specific gene modification approach will not be used directly for treating people with HIV or for cats with FIV, but it will help medical and veterinary researchers understand how restriction factors can be used to advance gene therapy for AIDS caused by either virus.

The method for inserting genes into the feline genome is highly efficient, so that virtually all offspring have the genes. And the defense proteins are made throughout the cat’s body. The cats with the protective genes are thriving and have produced kittens whose cells make the proteins, thus proving that the inserted genes remain active in successive generations.

Search: TRIMCyp, cats, felines, kittens, FIV, HIV, fluorescent, green, Mayo Clinic

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