Artificial virus gets into your genes

The trouble with genetic engineering is you need a carrier, or vector, to get the genes into the host species--whether Echerischia coli or Homo sapiens. The most adaptable vectors have tended to be crippled cold viruses. In practice these carry their own hazards and not surprisingly trigger public discomfort.

Jon Wolff and his colleagues in the Department of Pediatrics and Medical Genetics at the University of Wisconsin, Madison have now come up with an artificial virus based on liposomes, the molecular equivalent of soap bubbles--self-assembling spheres--with a hollow interior big enough to carry a coil of DNA, which should improve the passage of therapeutic genes into a patient's defective cells. (Nature Biotechnology, 1996, 14, 760)

Previous researchers have built similar structures to replace adenoviruses, which cause the common cold, as the vector. Wolff's new approach involves building in pH sensitivity to the liposome to improve on the approach.

He and his team built various liposomes using lipid surfactants containing a positively charged amine head group, such as aminopyridyl and imidazolyl, and long hydrocarbon chains. They found that they could carry circular pieces of DNA, known as plasmids inside the resultant liposomes.

They have tested how well their artificial viruses work in carrying their DNA payload into living cells, but so far only in the test-tube. They found that the positive charge allows the liposome to bind to the surface of the cells just as a real virus might. "The acid environment in certain parts of the cell (endosomes) enhances the amount of plasmid DNA carried across the cell membrane into the cell," explains Wolff. The researchers say a similar process occurs when an adenovirus, for instance, infects a cell.

"A greater understanding of how the DNA-liposome complexes form and interact with cells is the basis for improving delivery efficiency", says Wolff, "This should allow gene therapy to realise its full potential."

Glowing plants alert farmers to infection

It's midnight down on the farm. The farmer is surveying his crops and can see an eerie blue glow emanating from several clumps of plants scattered randomly throughout his fields. He is worried-the plants are obviously under stress. This item has been given its own page within the Sciencebase Science Blog under the heading Shining Unhappy Plants.

Getting under your skin

Changes in pH and temperature often accompany tumour growth or a failed oxygen supply to an organ. Getting a pH meter or a thermometer inside is not the most convenient of procedures despite the latest keyhole techniques.

Two groups of researchers have now turned to spectroscopic effects to make compounds whose NMR spectra change dramatically with changes in temperature, pH and concentration of damaging hydroxyl radicals. The compounds, they believe, could be given as a pill or injection and used in conjunction with magnetic resonance imaging (MRI) to measure the organ's vital statistics. MRI scanners measure NMR spectra so building a pattern of internal pH or temperature is a question of applying computer software to translate the spectrum into a map of the organ being monitored.

Silvio Aime and his colleagues in the Department of Chemistry at the University of Turin have developed a simple water-soluble compound based on ytterbium as a pH meter. (Chem Commun, 1996, p 1265).

According to Aime, the ytterbium is trapped in a tetraazacyclododecane ligand and the resulting complex has a very pH-dependant spectrum, which is little affected by temperature changes.

Klaus Roth and his team at the Free University in Berlin, on the other hand, have developed an analogous NMR thermometer based on the very effect Aime and his colleagues have avoided: the change in spectrum that accompanies a temperature rise. The German team hopes its probe will find use in controlling hyperthermia treatment for cancer where a laser is used to blast tumour cells but overheating of surrounding tissue can be a problem. (Angew Chem, 1996, vol 35, p 655).

Meanwhile, Aime has also applied the same idea of spectral shifts to developing an NMR indicator of hydroxyl radical levels (Chem Commun, 1996, 1509)

To sleep perchance to...

If you haven't nodded off reading this already, then you might be suffering from insomnia. Many people with sleep disturbances turn to drugs but these as always carry side-effects. US chemists think they have discovered a more natural way of controlling sleep which might one day lead to a new class of safer tranquilisers. (J Am Chem Soc, 1996, 188, 5938)

Richard Lerner and his team at the Scripps Research Institute in La Jolla California have built inhibitors of the enzyme oleamide hydrolase. This enzyme breaks down oleamide a compound formed in the body to trigger sleep. Once the oleamide disappears then your body knows you have had enough sleep. Trouble is an overactive hydrolase enzyme gets rid of the oleamide before that point hence the insomnia.

Lerner and his colleagues believe an inhibitor of this enzyme would trick the body into sleeping longer. "If you were to want to develop a sleeping aid, there's no better way to do it than to use the natural materials," says Lerner.

'Night 'night.