[Editors] MIT works toward safer gene therapy

[Elizabeth Thomson]

MIT News Office
Massachusetts Institute of Technology
Room 11-400
77 Massachusetts Avenue
Cambridge, MA  02139-4307
Phone: 617-253-2700
http://web.mit.edu/newsoffice/www

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MIT works toward safer gene therapy

--Biodegradable polymers replace viruses to deliver genes
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For Immediate Release
FRIDAY, SEP. 7, 2007
Contact: Elizabeth A. Thomson, MIT News Office -- Phone: 617-258-5402  
-- Email: thomson at mit.edu

PHOTO AVAILABLE

CAMBRIDGE, MA (09/07/2007) -- In work that could lead to safe and  
effective techniques for gene therapy, MIT researchers have found a  
way to fine-tune the ability of biodegradable polymers to deliver genes.

Gene therapy, which involves inserting new genes into patients' cells  
to fight diseases like cancer, holds great promise but has yet to  
realize its full potential, in part because of safety concerns over  
the conventional technique of using viruses to carry the genes.

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.

Gregory Zugates, a former graduate student in chemical engineering  
now at WMR Biomedical, Inc., is also a co-first author of the paper.

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. Most  
trials use viruses as carriers, or vectors, to deliver genes.

However, there are risks associated with using viruses. As a result,  
many researchers have been working on developing non-viral methods to  
deliver therapeutic genes.

The MIT scientists focused on three poly(beta-amino esters), or  
chains of alternating amine and diacrylate groups, which had shown  
potential as gene carriers. They hoped to make the polymers even more  
efficient by modifying the very ends of the chains.

When mixed together, these polymers can spontaneously assemble with  
DNA to form nanoparticles. The polymer-DNA nanoparticle can act in  
some ways like an artificial virus and deliver functional DNA when  
injected into or near the targeted tissue.

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.

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.

One promising line of research involves ovarian cancer, where the MIT  
researchers, in conjunction with Janet Sawicki at the Lankenau  
Institute for Medical Research, have demonstrated that these polymer- 
DNA nanoparticles can deliver DNA at high levels to ovarian tumors  
without harming healthy tissue.

Other MIT authors on the paper are Nathan Tedford, a former graduate  
student in biological engineering now at Epitome Biosystems; Linda  
Griffith, professor of biological engineering; Douglas Lauffenberger,  
head of biological engineering, and Institute Professor Robert  
Langer. Sawicki and Yu-Hung Huang of the Lankenau Institute are also  
co-authors.

The research was funded by the National Institutes of Health, the  
Department of Defense and the National Science Foundation.

The MIT Center for Cancer Research (CCR) was founded in 1974 and is  
one of eight National Cancer Institute-designated basic research  
centers. Its mission is to apply the tools of basic science and  
technology to determine how cancer is caused, progresses and responds  
to treatment.

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--Written by Anne Trafton, MIT News Office