Saturday, 17 January 2009

Targeting Therapies

Getting your drug therapy to the tissue that you want to treat is easy, the body's circulatory system is perfect for that. The problem occurs when the drug gets into other tissues and causes side effects, a long list of which can be found on the information sheet supplied with any drug.

There are a multitude of different ways of specifically targeting certain tissues or cells, and many new ways being developed with the use of new nanotechnology. One such method is being developed at the City University of New York. Here the drug is attached to a mesh of fatty acids, making it inactive. This mesh will disperse around the whole body like any other drug, but could be designed so that the drug can be detached from the mesh by an enzyme that is only present in the tissue being targeted. In this way the drug is only released in its active form at the desired location, thus limiting the chances of the drug getting into other tissues and causing side effects. This is in very early development and has yet to be proven outside of bench-top experiments, there is undoubtedly still a lot of work to be done to make this method work, but it shows us the kind of thinking going on in this area at the moment.

Here's some background to a different problem. DNA encodes the 'blueprints' for all the proteins your cells need to do their business, it is like the master copy. When the cell needs to make a protein it uses a slightly different chemical called RNA to make a copy of the gene, the cell then uses that copy to construct the protein. Many copies are made and transmit the message of how to construct the protein to the cellular machinery. When a cell is making a protein that it isn't supposed to, it can often cause disease. In the lab it is possible to block the RNA message by designing small segments of interfering RNA that stick to the RNA message. As the cellular machinery works its way along the message, making the protein as it goes, it reaches this interfering RNA segment and can't read the message anymore because it is blocked out and so the protein is never completed. Inject this interfering RNA into the body however, and you'll find it is destroyed pretty quickly in the blood before it ever reaches where it supposed to.

Calando Pharmaceuticals in California are testing in humans a kind of Trojan-horse system where the interfering RNA is packaged inside a nanoparticle studded with a molecule called transferrin. They chose this molecule because cancer cells are abnormally rich in receptors for that molecule, and when they detect it on the particle they will take the whole particle inside the cell. The acidity inside the cell is different to the blood, and this causes the particle to burst, releasing the interfering RNA into the cell where it can do its job. This technique is very promising as it can relatively easily be modified to target any receptors and deliver interfering RNA to all sorts of cells, not just cancer cells, and could potentially be adapted to deliver regular drugs.

A third approach is to make the cells produce the drug themselves. Viruses exist by infecting cells and making them produce all the proteins it needs, the virus just brings along the appropriate genes and the cell does all the work. Viruses are also very specific about the cells they infect, which is half the work already done for us. They are already being used selectively infect cancer cells, thereby killing them. Companies such as Oncolytics, Genelux and others are carrying out trials of this method. Viruses or artificial virus-like particles can be designed to deliver a gene for a specific enzyme that makes an active drug out of an inactive 'pro-drug' that is injected normally. This means the infected cell becomes a kind of drug factory at the precise location the drug is required, minimising the exposure of the rest of the body to that drug.

In ways such as these the treatments of the future will have a much reduced range of side effects, while at the same time being more effective and improving the quality of life of people suffering from chronic diseases.

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