An inherited disease caused by a single dominant gene. It typically develops between the ages of 35-50 and at present there is no cure.
Problems which are inherited.
The complete sequence of all 20,000-25,000 human genes. That is, which chromosomes they are in and whereabouts the gene appears on that chromosome's piece of DNA.
Growing cells under controlled conditions, generally outside of their natural environment.
Alternative forms of the same gene.
Molecules which contain a lot of stored energy built up of fatty acids and glycerol. Lipids include oils and fats
The main organ of the central nervous system made up mainly of grey matter
A surprising number of diseases are caused by problems in our genes. Now we have unravelled the sequence of the human genome, more and more such diseases are likely to be discovered. Genetic modification has opened the door to the idea that we might be able to cure or prevent these diseases by changing the very nature of our genes.
Much of the discussion about gene therapy involves the idea of replacing damaged genes with healthy ones which will code for the right protein in the right place. However, a new and rather different approach, which may be very effective for some genetic disorders, is the idea of gene silencing.
Gene silencing is a relatively new technique, only invented in the late 1990s. As a result of silencing, specific genes can be shut down so that they no longer produce a rogue protein. The silencing is brought about by preventing the expression of the gene. In 2006 Andrew Z Fire and Craig C Mello were awarded a Nobel Prize for their work in gene silencing.
Scientists have found that by injecting nematode worms with a double-stranded piece of RNA which corresponds to a particular gene, they can block its action. They have even been able to feed the RNA to the worms and show that it has the same effect.
From worms to people is a big leap, but scientists have found that small chunks of double-stranded RNA can indeed block the action of genes in human cells as can short bent pieces of RNA. Short hairpin activated gene silencing (or SHAGging, as the researcher called it!) worked to prevent the production of certain proteins in lots of different types of cells.
The next step is the most exciting. Researchers have managed to genetically modify cells so that they code for engineered short hairpin RNAs. This means they have created cells which produce their own gene silencing mechanism. What is more, these cells can pass this engineered ability on to their daughter cells as the cell culture grows and divides.
The potential for this in the treatment of diseases like cancer and AIDS is enormous. But in 2010 the first disease actually prevented using gene silencing was a respiratory infection caused by a virus known as RSV. This disease is usually mild in adults but it can be very serious in small children. A nasal spray containing RNA fragments to silence one of the viral genes, in tests, almost halved the numbers of people infected with the virus. This therapy is being tested on patients with lung transplants to protect them from infection. Hopefully soon it can be used to protect tiny babies from the disease.
It is for genetic problems such as Huntington’s disease that gene silencing offers the most immediate hope of effective treatment. The genetic mutation which causes Huntington’s disease results in the cells making too much of a specific protein. This causes the symptoms of the disease. Scientists in the US have been able to silence this gene in mice using gene therapy. It will be impossible to silence the gene completely in people, because brain cells cannot survive without the normal amount of the protein. However, affected people usually have one normal allele and one allele for the condition. If the affected allele can be silenced, leaving the normal allele working, then the symptoms of Huntington’s disease could be prevented.
You can learn more about how Huntington's disease is passed on in the genes and inheritance resource.
One of the biggest issues with silencing genes is delivering the RNA interference sequences to the right place at the right time. Work using nanoparticles based on lipids similar to the cell membrane amongst other techniques is enabling scientists to deliver the RNA sequences to where they are needed. A number of proof of principle studies have been carried out – now scientists are looking towards pre-clinical trials. There is still a lot of work to be done before treatments for diseases like Huntington's are available – but gene silencing means there may be light at the end of the tunnel.