mito article

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I just found this article while doing a search today. It's from 2001. Has anyone heard anymore about this?

Antiseptic May Target Mitochondrial Disease

Certain mitochondrial diseases are currently beyond the reach of gene therapy, but a chemical commonly used as an antiseptic might be the magic bullet for that problem.

A DQAsome is a hollow capsule formed from many bolaform-shaped DQA molecules (highlighted). The capsule might make an ideal gene therapy vector for mitochondrial diseases.

Gene therapy — the delivery of corrective genes to make up for a genetic defect — holds promise for treating most genetic diseases, and in some cases, is already being tested in clinical trials. But some mitochondrial diseases are off-limits to current gene therapy techniques because they're caused by defects in hard-to-reach genes.

Most of our genetic material (DNA) is housed within the nuclei, the control centers found in nearly all our cells. But some DNA is housed in the mitochondria, the tiny powerhouses that provide energy to cells. Defects in mitochondrial DNA can cause energy deficits that lead to the extreme fatigue and weakness characteristic of mitochondrial muscle diseases.

While scientists have achieved success in targeting therapeutic genes to nuclei, it's more challenging to get genes into mitochondria. The problem lies in the gene delivery vehicles, or vectors, says Volkmar Weissig, a biochemist at Northeastern University in Boston.

In gene therapy, a vector's first task is to penetrate the cell's outer membrane, or skin. Once inside the cell, the vector must breach a second membrane surrounding either the nucleus or the mitochondrion, all the while holding on to its genetic payload.

The most commonly used vectors for gene therapy are viruses and synthetic compounds called liposomes, hollow spheres composed of an outer shell of lipid (the same type of chemical that makes up cell membranes). Viruses, says Weissig, naturally infect cells and introduce foreign genes into nuclei, but apparently can't send genes to mitochondria. With a composition similar to cell membranes, liposomes can penetrate cells, but they usually release their DNA into the cellular space shortly afterward.

To make mitochondrial gene therapy feasible, Weissig is using MDA support to custom-design a vector from a lipidlike, antiseptic chemical called dequalinium (DQA). A single unit of DQA looks like a traditional Native American weapon called a bola, and this bolaform shape allows DQA to form liposome-like capsules called DQAsomes. DQAsomes can be filled with DNA, and thus might be ideal weapons against mitochondrial diseases, Weissig suggests. So far, he's shown that the DQAsomes can selectively target DNA to mitochondrial membranes.

"This is basic research" that won't immediately lead to treatment for mitochondrial disease, Weissig says. But it's a significant step in the right direction.