October 17, 1997
Contact Ron Brown LSU News Service 504 388-3867 e-mail: [email protected]
BATON ROUGE -- Vaccinations may ultimately take their place beside leeches in medical history if promising methods of inserting DNA into animal tissues works out.
Gus Kousoulas, professor of veterinary microbiology and parasitology at LSU's School of Veterinary Medicine, is working on a way of replacing standard vaccinations by putting DNA directly into a patient's cells. The new delivery system is an aspect of gene therapy known as genetic immunization.
Kousoulas is researching the use of synthetic polymers, called poloxamers, to deliver genes into muscle cells.
"Poloxamers encapsulate the DNA, protect it and deliver it into the muscle," he said. "We can get 10 times as much DNA into a cell using poloxamers as we can injecting naked DNA." Much of the unprotected DNA which is injected into the body is destroyed or lost, he said.
Traditional vaccination injects bits of protein -- usually from a virus or bacteria that has been killed or weakened -- into the bloodstream. When the immune system encounters this foreign protein, it produces antibodies and "killer" cells programed to recognize the protein's shape, search it out and destroy it. If the body has not been exposed to a particular disease, it takes a while to generate antibodies and killer cells, which gives the invading pathogen plenty of time to do damage.
"In the past it has been often difficult to create these vaccines because they must be highly purified and must not cause any damage. Even now, a certain percentage of vaccines cause damage.
"But if, instead of injecting proteins, you can inject genes -- the DNA that ultimately makes proteins -- into the muscles, they are taken up by the cells, and the DNA makes the RNA which makes the proteins. When the protein is expressed, you stimulate the immune response.
"DNA is easy to make in large amounts, is easy to purify and is cost effective," Kousoulas said.
The DNA stays in the body four to six months, until the cell that took it up dies and is eliminated. But that is enough time to generate an immune response, Kousoulas said.
Experiments currently being done on animals indicate that injecting DNA into the tissues has no serious side effects, he said.
The fact that genes injected directly into the body would be absorbed by the cells was discovered by chance in 1993. It has now been shown that eye drops, nasal spray and even mouthwashes are effective in delivering DNA.
Kousoulas is working with Vaxcell Inc., based in Norcross, Ga., on the poloxamer delivery system. To test the efficiency of different poloxamers and different sizes of poloxamers, he mixes them with DNA and injects the solution into mice. Later he inoculates the mice with high dosages of the herpes virus to determine their immune response.
Two other benefits associated with DNA-based vaccines include the ability to target that arm of the immune system which is activated by a particular disease and to minimize inflammation.
"Sometimes more of the damage associated with a disease is caused by the immune system's response than by the pathogen itself. DNA can be programed to express anti-inflammatory proteins such as interlukin-10, which will keep down inflammation," Kousoulas said.
A spinoff from Kousoulas's research has already come in the form of two patents he has filed for a DNA-based vaccine against psittacosis, an upper respiratory disease, and for genetic immunization using poloxamers. Psittacosis generally infects exotic birds, such as parrots, but can also cause acute respiratory problems in humans.
# # #
RSS