A new method of inserting genes into brain cells could
greatly simplify the search for brain-disorder
treatments, according to research reported this month.
It uses an array of electrodes, each 100 micrometers
wide, to inject genetic material into individual
neurons. The technique’s inventor thinks it could be
the key to examining thousands of genes for answers to
vexing neurological problems, with the hope of one day
performing gene therapy in the brain.
Gene therapy involves inserting genetic material into
a malfunctioning cell to alter its activities and cure
disease. Doing this in the brain would be particularly
challenging, mainly because very little is known about
how networks of neurons function or how to safely alter
the components of such a network.
Generally, genetic engineers start by injecting into a
target region a virus that has been modified to
include human genes. In a technique called transfection,
the virus will infect some cells and deposit its genome
inside them. If things go as planned, the human genes
inserted by the virus replace or restore a nonfunctional
gene in the neuron. But viral transfection is laborious
and difficult to control: a virus will transfect
neurons more or less arbitrarily. “If you transfect
the wrong neuron, you can change the overall function in
a part of the brain in a really dramatic way,” says Jit
Muthuswamy, a biomedical engineer at Arizona State
University, in Tempe.
Muthuswamy has invented a technique that uses tiny
electrodes, instead of a virus, to slip genetic material
into cells [see "Shock
Treatment"]. The electrodes send a pulse of
electricity that briefly blasts holes in the neuron’s
membrane. Segments of genetic material coating the
electrodes can then enter the cell before it seals up again.
Each electrode can also monitor the injected neuron’s
electrical activity, such as the rate at which it
pulses. The gene transfer might alter that activity in
a recognizable way. “This is about delivering genes in
a much more controlled fashion,” Muthuswamy says. He
and graduate student Tilak Jain describe the technique
in the February 2008 issue of IEEE Transactions on
Biomedical Engineering.
For now, the array is intended only for brain cells
that have been grown atop it, not yet in humans or even
laboratory animals. But that’s enough for some
scientists. “It’s really hard for us to make sense of
any nervous-system network,” says Julie Kauer, a
molecular pharmacologist at Brown University, in
Providence, R.I., who studies individual neurons. With
the array, “you could see if something affects a
neuron’s firing rate or changes its firing pattern.”
The microelectrode arrays can also target specific
types of neurons in a network. Different kinds of
neurons have different electrophysiological
properties. The electrodes can read these properties as
if they were a neuron’s signature. Thus only neurons
with the proper signature might receive a zap from the
electrode.
Danilo Tagle, a program director at the National
Institute of Neurological Disorders and Stroke, in
Bethesda, Md., suggests that the arrays will help
scientists understand neuron interactions by letting
them alter one neuron at a time and watch how other
neurons respond. “This technology can be adapted to
answer all kinds of gene-therapy questions,” Tagle says.