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Sugar capsules used in efforts to fight disease

15.11.2006
A group of scientists from University of Aarhus in Denmark have achieved a breakthrough in the race to find a universal cure for cancer, viral diseases and hereditary disorders.

By encapsulating medicine in billions of microscopic sugar cubes, the cells of the body are tricked into absorbing pharmaceuticals that could not normally be transported across the cell membrane. And this contains a number of perspectives. In their experiment, the scientists fill the sugar cubes with a DNA copy called siRNA, the function of which has just led to the award of the Nobel Prize in Physiology or Medicine 2006.

This substance can switch off faulty genes selected among thousands of cells and thus cure the diseases caused by these genes. This discovery has been published in acclaimed journals and the first experiments on humans can begin in four to five years. Chitosan is a sugar that can be a very effective weapon in the fight against arthritis, influenza, hepatitis and many of the cancer diseases that plague the ageing population of the western world. This is not because the sugar itself cures these diseases, but because it can transport healing medicine to the body’s sick cells – in the form of extremely small nanocapsules with a diameter of just one hundred thousandth of a millimetre. After delivering its load directly into the cells affected, the chitosan sugar is broken down in the body and disappears without a trace.

This discovery was made by a group of researchers at the Interdisciplinary Nanoscience Center (iNANO) at the University of Aarhus, and they have just published an article in the prestigious journal Molecular Therapy. In this article, the scientists describe their experiments on mice, and the first preclinical trials on humans will probably begin in three to four years.

Mice genetically spliced with jellyfish

The experiment itself involved switching off a particular gene contained in the genome of the mice. This task is complicated by the fact that all the cells in an organism contain a copy of the genome, and that the genome contains tens of thousands of genes. However, an adequately large number of nanocapsules can solve this task. It would be reasonable to wonder how the scientists can see how they have switched off a particular gene in their mice, but in this case, it is actually very simple. A gene from a green jellyfish found in the Pacific Ocean was first inserted into the mice, and this turned them green from the outside in. When a researcher subsequently gave them new medicine, they returned to their normal colour because the gene was made ineffective. The scientists anticipate that within six to ten years, it will be possible to treat humans on a large scale by switching off particular genes associated with many diseases in which one or several genes no longer function as intended – thus curing the disease. Arthritis is just one example, and the researchers’ experiments regarding the treatment of arthritic mice are very promising. Viral infections are also a potential target for the nanocapsules. In such cases, the treatment is not aimed at the genes in the cells of the body, but at the genome of the disease itself. By switching off the genes that make the influenza virus or HIV capable of reproducing, it will be possible to combat the virus.

Gentle alternative to chemotherapy

To understand the advantages of targeted treatment using nanocapsules in the future, it should be compared with traditional medical cancer treatment, for example. Chemotherapy can be administered orally or intravenously, but will invariably suffer from the same weakness – healthy cells are also affected by chemotherapy, and this results in a number of well-known and very uncomfortable side effects, such as hair loss, nausea and a depressed immune system. Millions of patients throughout the world know the consequences of chemotherapy only too well. If the medicine could be encapsulated in microscopic containers that went through the body unnoticed, and finally delivered their load at the point of the illness, this would minimise the side effects and represent major progress in the treatment of cancer. And the researchers from Aarhus have come a long way as far as this target is concerned, by encapsulating the active substance in chitosan sugar nanocapsules. Because chitosan occurs in nature and is completely safe for the body, the capsules can be administered via an oral spray that leads them into the lungs, out into the blood vessels and on to the cells. Each cell would normally resist the entry of the foreign substance, but this is not the case with the nanocapsules because the cells cannot recognise the pharmaceutical load inside them, but think that a tasty little sugar snack is on its way. The capsules are allowed to enter the cell, where the enzymes inside the cell chop the chitosan sugar into pieces and the medicine is thus smuggled into its destination.

The hottest item in biotechnology

The contents of the nanocapsules are elongated molecules called siRNA, which can switch off the activity in the sick cells by means of a mechanism called RNA interference. The molecules themselves represent ground-breaking technology and have recently been the reason the Nobel Prize in Physiology or Medicine 2006 was awarded to scientists Andrew Fire and Craig Mello. Their RNA interference utilises some quite distinct mechanisms in the way the cell functions. The body’s basic building blocks are the proteins, and the way they are built up is described in the genes contained in the genome. However, these genes cannot build the proteins themselves, but send instructions from their position in the cell nucleus to the outer cytoplasm of the cell via a piece of messenger RNA. Because these pieces of messenger RNA are specific for every gene, the scientists design special siRNA to find the messenger RNA from the sick cell, adhere to it and destroy it. In this way, the sick gene is also rendered useless. What is so brilliant about this technique called RNA interference is that the body’s sick genes are passivated without affecting anything else. RNA interference is probably the hottest item in biotechnology at present, with loads of high-risk capital to back it up. Within the course of a few years, this technology will also put viruses out of action by paralysing several of their genes that are essential for survival and reproduction.

A universal cure for disease

The greatest problem confronting this very promising treatment has so far been that the body effectively breaks down siRNA molecules before they reach their target, but this barrier is about to be removed. The scientists from iNANO in Aarhus have effectively demonstrated that the task can be solved using some simple, protective capsules made of a well-known sugar. Many other groups of researchers throughout the world are working on similar technology, but iNANO is now at the forefront of this research, which can become a universal cure for a myriad of diseases within a few years. Clinical experiments using nanocapsules and siRNA on humans will begin in just a few years and the experts are starting to have extremely high expectations.

Dan Frederiksen | alfa
Further information:
http://www.nat.au.dk/default.asp?id=11886

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