Microchip Enables Electronic Gene Injection

Tiny electrodes could bring gene therapy into the brain

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.

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