mito article

[Guest guest]

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.