September 08, 2007
MIT Polymers Might Make Better Gene Therapy Delivery Packages

After decades of experimentation scientists still do not have good ways to deliver gene therapy into cells in humans or other animals. Gene therapy is a crucial piece of the puzzle needed to cure many diseases (notably cancer) and to rejuvenate old bodies. Gene therapy is especially needed for brain rejuvenation. For the rest of the body cell therapies and replacement organs will provide easier ways to make worn out parts young again. But most neurons need to be repaired rather than replaced. So we need brain gene therapy to prevent our minds from growing old. With this thought in mind, recent MIT research looks promising for a better way to deliver gene therapy.

The new MIT work, published this week in Advanced Materials, focuses on creating gene carriers from synthetic, non-viral materials. The team is led by Daniel Anderson, research associate in MIT's Center for Cancer Research.

"What we wanted to do is start with something that's very safe--a biocompatible, degradable polymer--and try to make it more effective, instead of starting with a virus and trying to make it safer," said Jordan Green, a graduate student in biological engineering and co-first author of the paper.

The polymers self-assemble with DNA and package the DNA inside them.

Over 1,000 gene therapy clinical trials have failed so far.

Gene therapy has been a field of intense research for nearly 20 years. More than 1,000 gene-therapy clinical trials have been conducted, but to date there are no FDA-approved gene therapies.

A string of successful gene therapy clinical trials will some day mark a really big turn in the road toward the development of much more powerful medical treatments.

Key to this advance was the development of techniques to rapidly create and test large numbers of variations in polymers.

The researchers developed methods to rapidly optimize and test new polymers for their ability to form DNA nanoparticles and deliver DNA. They then chemically modified the very ends of the degradable polymer chains, using a library of different small molecules.

"Just by changing a couple of atoms at the end of a long polymer, one can dramatically change its performance," said Anderson. "These minor alterations in polymer composition significantly increase the polymers' ability to deliver DNA, and these new materials are now the best non-viral DNA delivery systems we've tested."

The polymers have already been shown to be safe in mice, and the researchers hope to ultimately run clinical trials with their modified polymers, said Anderson.

Even if this delivery vehicle turns out to work well to get DNA into cells that does not mean that a gene therapy which uses this delivery vehicle will be safe. Once the DNA gets into a cell it can integrate into a chromosome at a location that causes eventual cancer. So there's a second problem of how to get the newly introduced DNA to play nice with the cell it gets inserted into. Gene therapy is hard.

Viruses as gene therapy carriers are problematic because they usually cause an immune response. Plus, the amount of DNA which these polymers can carry looks to be larger than the amount that virus coatings can carry into cells.

Non-viral vectors could prove not only safer than viruses but also more effective in some cases. The polymers can carry a larger DNA payload than viruses, and they may avoid the immune system, which could allow multiple therapeutic applications if needed, said Green.

The researchers report success in getting their polymers to carry DNA into ovarian tumors. Gene therapy for cancer cells holds the promise of either reprogramming the cells to stop dividing or to even tell the cells to commit suicide.

Share |      Randall Parker, 2007 September 08 04:11 PM  Biotech Gene Therapy

Rob said at September 9, 2007 11:01 AM:


I don't know if you already new this, but Aubrey de Grey has a book out "Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime"

Randall Parker said at September 9, 2007 11:22 AM:


I'm aware of Aubrey's new book and even got an email asking if I want a complimentary review copy. I said yes. That was a week or two ago. Haven't seen the book yet. Looking forward to writing up a post about it when the book gets here.

Rob said at September 9, 2007 2:41 PM:

It's not bad so far, I'm about 50 pages in. I'm not fond of his writing style, though maybe I'll get used to it. He's definitely working on the last third of Tim Leary's SMI^2LE. At worst, he'll convince some people that LE is a possibility.

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