Naked DNA Vaccination
cowboy
By JUDY SIEGEL
HAIFA (September 24) - An important and innovative method developed at the
Technion using genetic engineering to "vaccinate" the body with DNA has
proven itself successful in mice as a model for treating autoimmune
diseases, such as multiple sclerosis, rheumatoid arthritis, and type-I
diabetes.
Dr. Nathan Karin and colleagues of the Rappaport Faculty of Medicine's
department of immunology have just published an article on their research in
the latest issue of Gene Therapy.
In autoimmune diseases, the body's immune system attacks tissue that it
mistakenly recognizes as "enemy" or "foreign" and triggers an inflammatory
process.
In MS, the myelin coating of neurons is attacked, causing the nervous system
to short circuit, with resulting neurological damage; in rheumatoid
arthritis, the connective tissue is harmed; while in juvenile-onset
(insulin-dependent) diabetes, beta cells in the pancreas that produce
insulin are destroyed.
Karin's team is the first to develop a genetic treatment that prevents the
immune system from creating an inflammatory process when the body's own
tissue is misidentified as foreign. The Technion technique, which has not
yet been tested in humans, is unique in that it uses tools whereby the
immune system attacks its own tissue to "re-educate" it and prevent it from
causing harm.
Karin's group injected a viral vector (carrier agent) into which segments of
DNA were engineered into the leg muscle of lab animals. Only about four or
five injections were needed. These segments code for pro-inflammatory
proteins connected to the auto-immune diseases.
Using this technique, which is called "naked DNA vaccination," the
researchers succeeded in breaking down the passive immunity to some proteins
important in the inflammatory process and create "immunity memory" against
these substances. As a result, antibodies against the proteins are created,
and the inflammatory process is quickly controlled. A Haifa scientific
"incubator" will be established to complete the animal experiments and
prepare for eventual clinical trials on patients.
Karin told The Jerusalem Post he has been working on the technique for three
years, some of it as post-doctoral work at Stanford University in the US.
Prof. Irun Cohen, director of the Minerva Center for Research into
Autoimmune Diseases at the Weizmann Institute in Rehovot, commented that the
concept of naked DNA vaccination is "very significant. It's another example
of how the immune system can be enlisted to regulate its own affairs. Using
it on patients at this point would be very premature, as we don't know about
side effects or if it would work in humans as it has in mice. We have to
know more about the mechanisms.
"A possible problem could be that the technique knocks out the immune
response, but if you do this completely, the body could be susceptible to
infection from pathogens from the outside. It needs selective regulation so
that the immune system can still attack outside invaders. But down the line,
I have no doubt that Dr. Karin's approach will bring about important
therapeutic reagents and more knowledge."