IR techniques aid gene
delivery
Ultrasound bursts contrast
microbubbles
By Jane Lowers
In gene therapy, as in stand-up comedy, successful material depends heavily
on the delivery. So far, delivery is proving to be one of the field’s
toughest challenges. Capable of creating increasingly sophisticated strips of
genetic code destined for specific targets within the body, gene therapists are
finding it difficult to make the vectors stay where they’re wanted and
insert their payload into the appropriate cells.
“That’s the Holy Grail for this field—successful targeting of
the vector to the specific tissue and having it leave other things alone,”
said Dr. Nelson Wivel, deputy director of the University of Pennsylvania’s
Institute for Human Gene Therapy. “We’re not there.”
For radiologists, some of the best delivery methods to date are old
favorites: via catheter threaded under fluoroscopy into the hepatic artery, for
example, or via direct needle injection for metastases in the liver.
Dr. Evan Unger, an Arizona radiologist, is taking another approach, cranking
up ultrasound to burst contrast microbubbles with genes bound to their surface.
[Fig. 1] The technique is being tested in animal models for
cardiac applications, and Unger, founder of Imarx, is interested in seeing
whether the same principle can be used to deliver other cancer-fighting
drugs.
“If you look at a needle in a tumor, first of all it’s invasive,
and you don’t get good distribution because the injection doesn’t go
very far,” he said. “Microbubbles can move right up into microvessels,
and popping the bubbles releases a shock wave to drive the genes into the
cells.”
There’s some basis for the argument, Wivel said. An in vitro technique,
electroporation, uses electrical current to nudge genetic material into
cells.
“For cancer in particular, gene therapy is always going to be an
adjunct, and that’s where radiologists will play a role,” he said.
“You’re never going to get it into every last cell, but if you can
combine it with other techniques, you may help amplify immune response as
well.”
