March 26, 2007
Thin Films Deliver Gene Therapy

Thin films help deliver gene therapy.

David M. Lynn and his colleagues have created ultrathin, nanoscale films composed of DNA and water-soluble polymers that allow controlled release of DNA from surfaces. When used to coat implantable medical devices, the films offer a novel way to route useful genes to exactly where they could do the most good.

Lynn, a UW-Madison professor of chemical and biological engineering, has used his nanoscale films to coat intravascular stents, small metal-mesh cylinders inserted during medical procedures to open blocked arteries. While similar in concept to currently available drug-coated stents, Lynn's devices could offer additional advantages. For example, Lynn hopes to deliver genes that could prevent the growth of smooth muscle tissue into the stents, a process which can re-clog arteries, or that could treat the underlying causes of cardiovascular disease.

What is our biggest need for gene therapy? Brain rejuvenation. That's right. Brain rejuvenation. For most of the rest of the body the development of cell therapies and means to grow replacement organs will do most rejuvenation. But in the brain we need to repair each neuron. Stem cell therapies will still deliver benefits for the brain, for instance by repairing blood vessels. But we need to turn back the biological clock on our about 100 billion neurons per brain.

The polymers gradually dissolve once placed in the body. Then the DNA they contain seeps out and some of it presumably enters cells.

As it turns out, making the DNA-containing films is relatively straightforward, Lynn says, but "getting [the DNA] back out of the films is the hard part."

The secret to films that release DNA is in the choice of the polymer and the layer-cake design. The researchers alternate layers of DNA with layers of a polymer that is stable when dry but that degrades when exposed to water. Because the polymers carry a positive electric charge that is attractive to DNA, each polymer layer also "primes" the surface to accept the next layer of DNA. While electrostatic forces between the layers keep the film stable in dry, room-temperature conditions, the polymers break down easily in a wet biological environment - like the inside of a patient's body.

Here's the really cool part. Lynn's group is designing different variations on thin films that will deliver gene therapies at different speeds and even deliver different genes in sequential order.

Lynn's laboratory has engineered a whole toolbox of different polymers to fine-tune the DNA delivery properties of their films. Using the layering method, they can control the amount of DNA by adding more layers, or can even layer multiple ingredients in a specific order. Tweaking the polymer structure slightly can change how quickly the films erode and thus how long cells are exposed to the gene therapy. "We ultimately need an effect prolonged enough to be therapeutically relevant - whatever time scale that might turn out to be, " explains Lynn.

The value of accelerating gene therapy development is enormous. Gene therapy used to make brains young again will some day boost economic productivity by trillions of dollars per year. Making that day come years sooner would gain us a total of tens of trillions of dollars or more. We underspend on body and brain rejuvenation research.

Share |      Randall Parker, 2007 March 26 10:23 PM  Biotech Gene Therapy


Comments
Wolf-Dog said at March 27, 2007 12:23 AM:

So far, Gene Therapy has been unsuccessful in the sense that on many occasion, the DELIVERY of the gene to the precise location has been a failure. As a result, many people who volunteered for Gene Therapy, died in horrible ways, due to the side-effects that the insertion of genes produces, for it is difficult to avoid "delivering" the therapy to wrong locations.

This is why there is research on "Zinc-Fingers" which promise to make this miraculous step of delivering the gene therapy exactly to the location where it is needed.

http://www.eastbayexpress.com/2007-02-28/news/the-gatekeeper/

http://www.nature.com/gt/journal/v12/n19/full/3302572a.html

Brett Bellmore said at March 28, 2007 4:02 AM:

I remain convinced that the best option for delivering genetic mods to the brain would be a modified intracellular parasite. In one already existing package you've got the capacity to cross the blood/brain barrier, travel through tissue, distinguish cell types, and enter cells without disrupting them. A bit of engineering to reduce virulence, and add some reproductive controls/failsafes, and you've got a vector which could carry whole artificial chromosomes to designated neuron types. Or even just travel to the cells, and become resident organelles. Short of full blown Drexlerian nanotechnology, you're not going to do better.

Randall Parker said at March 28, 2007 5:47 PM:

Brett,

The idea has appeal. Your proposed organism could contain a copy of DNA encoded with an error correcting code. It could go from cell to cell and rewrite chromosomes to fix all the accumulated damage since the last time it visited. Put, say, 100,000 in a brain and over a period of a couple of decades they'd each visit and fix 1 million neurons for a total coverage of 100 billion neurons. Then they'd start all over again.

Wolf-Dog said at March 28, 2007 8:02 PM:

But how reliable is the use of these organisms to distinguish where to deliver the gene therapy?
We must be very careful to avoid choosing the wrong target.

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