March 22, 2006
Nanoscale Honeycomb Lipid DNA Complexes For Gene Therapy

A UC Santa Barbara team has developed a new way to deliver gene therapy using lipids in a novel packaging arrangement.

Lipid DNA complexes are attracting increasing attention as non-viral DNA delivery vehicles. They have been described as one of the "hottest new technologies" for gene therapy, accounting for nearly 10 percent of ongoing clinical trials.

Lipids are molecules with two parts, a water-liking "headgroup" and oily tails that assemble together to avoid water. Lipids, along with carbohydrates and proteins, constitute the main structural material of living cells.

The novel lipid molecule created at UC Santa Barbara has a tree-shaped, nanoscale headgroup and displays unexpectedly superior DNA-delivery properties. "It generates a honeycomb phase of lipid DNA complexes," said Cyrus R. Safinya, a professor of materials; of molecular, cellular and developmental biology; and of physics at UCSB. The new molecule was synthesized in Safinya's laboratory by first author Kai K. Ewert, a synthetic chemist who is a project scientist in the research group.

"We've been trying to get a lipid-based honeycomb lattice for a long time," said Ewert. The structure of lipid DNA complexes strongly affects their ability to deliver DNA.

"Complexes containing sheets or tubes of lipids have been known since Safinya's group found these structures in 1997 and 1998, but no one had ever seen nanoscale cylinders such as the ones in our honeycomb lattice," Ewart said. The scientists proved the formation of this novel structure with X-ray scattering experiments. Ewert designed and synthesized the new lipid by manipulating the size, shape and charge of a series of molecules. He explained that the new lipid molecule has 16 positive charges in its tree-shaped headgroup, the largest number by far in the field of gene delivery.

The process of delivering a gene of interest into the cell is known as "transfection." In the paper, the authors describe transfection efficiency studies carried out in four cancer cell lines using the new molecule. Two of these are mouse cell lines and two are human cell lines. The honeycomb structure turned out to be highly effective.

The use of cancer cells as targets for gene therapy experiments makes sense for two reasons. First off, if the right genes could be delivered into cancer cells then the cells could be instructed to stop dividing and even to kill themselves. Second, since gene therapy still has considerable risks it makes sense to test gene therapies against diseases that are fatal. Lots of people are dying of terminal cancer every day. The risk that a gene therapy might itself some day cause cancer matters less to people who are already dying of cancer. Better to trade a fatal cancer of today for a (probaly less likely to be fatal) potential cancer 10 or 20 years hence.

Their approach is an improvement on efficiency as compared to existing approaches.

"Our new gene carrier shows superior transfection efficiency compared to commercially available carriers," said Ewert. "However, the most surprising result was obtained with the mouse embryonic fibroblast cells known as MEFs. These are empirically known to be extremely hard to transfect."

Safinya added: "Our data confirm that MEFs are generally hard to transfect. And the new molecule is far superior for transfection of these cells as compared to commercial lipids."

Gene therapy doesn't get the attention it deserves because it does not create ideological divisions and disagreement even beginning to approach those that have sprung up around human embryonic stem cell research. But gene therapy is probably at least of equal importance to cell therapy. The ability to upload patches to our genetic programs would be a boon. Cancer, heart disease, and general aging could be attacked with gene therapies. Ditto for many other diseases. Many genetic diseases could be cured with gene therapies.

Share |      Randall Parker, 2006 March 22 10:04 PM  Biotech Gene Therapy

Lou Pagnucco said at March 23, 2006 8:35 AM:

Does anyone know if a similar approach can be use for delivery of RNAi or anti-sense RNA?

detribe said at March 23, 2006 6:37 PM:

Interesting Randall. Maybe you could emphasise the point that new transfection/gene delivery methods are very versatile. Any gene could be delivered, and many diseases other than cancer are on the list for therapy. Eg diabetes, Parkinsonism.
GMP Pundit

Randall Parker said at March 23, 2006 8:12 PM:


I probably ought to do posts explaining hwo gene therapy could treat many different diseases. You know that and I know that. But I tend to forget how many things are just not common knowledge.

Cell therapy and replacement organs will solve a lot of problems. But we especially need gene therapy for brain aging repair to make our existing neurons young again.

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