Gene therapy could turn airways into a medicine pump.
Gene therapy that converts a patient's lungs into a living, breathing medicine factory could one day eliminate regular drug doses for diabetics and haemophiliacs, new studies suggest.
Gene therapy adds working genes to tissues that have defective ones. But most research has focused on supplying lung genes to sick lungs and muscle genes to ailing muscles.
In a new twist, James Wilson and his team at the University of Pennsylvania have added to mice lungs a gene that encodes the protein missing from some haemophiliacs' blood. For months thereafter the animals' airways produced the protein, called factor IX, at levels that would treat human patients1.
"The possibilities are endless," says gene-therapy researcher John Engelhardt of the University of Iowa in Iowa City. The lungs could be used to pump out virtually any therapeutic protein, he says, such as insulin or growth hormone.
Currently, type I diabetics take daily injections of insulin, and haemophiliacs need regular infusions of factor IX. Wilson's team also demonstrated the technique's potential to supply erythropoietin, a substance that stimulates the production of red blood cells and is used to treat chronic kidney failure.
The lung is an ideal organ for churning out drugs. Patients could inhale therapeutic genes easily in aerosol sprays. Once taken up into the cells of the air sacs, a rich supply of blood could carry off any medicinal protein that they secrete.
The idea of a living drug factory is not new, but scientists have struggled to deliver enough genetic material to the lung to produce protein at therapeutic levels. Wilson's team uses new strains of adeno-associated virus that efficiently inject genes into lung cells.
“This is the first really successful effort Terry Flotte , University of Florida”
"This is the first really successful effort," says geneticist Terry Flotte of the University of Florida in Gainesville. He and others are turning muscle and liver into drug factories by injecting gene-bearing viruses into them; clinical trials using the liver to make factor IX are already underway.
Some researchers have proposed co-opting the gut in a similar way, or making artificial 'organoids' that could be implanted under the skin. It is too early to say which of these options will become the factory of choice, says Flotte. Researchers have yet to prove that proteins made in abnormal places still work normally and do not cause dangerous immune reactions.
Aurricchio, A. et al. Noninvasive gene transfer to the lung for systemic delivery of therapeutic proteins. The Journal of Clinical Investigation, 110, 499 - 504, (2002).
University of Florida