A new technique for silencing and activating genes could transform the speed and efficiency with which genetic diseases are treated.
Developed by UK biotechnology company Silence Therapeutics, it works by creating RNA – the molecule responsible for controlling gene expression in nature – in a synthetic form, and using it to influence how our genes are activated.
Every gene in the body codes for the creation of a protein, but sometimes a defection can result in that gene not being expressed properly, which causes disease. It is these defections that gene modification attempts to correct.
“There are two ways of targeting genetic diseases – upregulation of a gene and downregulation. In one, you create more protein, and in the other you create less,” Ali Mortazavi, chief executive of Silence Therapeutics, told City A.M. in an interview.
By selectively interfering with the way DNA is expressed, the technique opens the door to a new and more efficient way of treating diseases such as cancer, infectious diseases, and a whole host of rare but deadly disorders, many of which are too difficult or expensive to treat using other methods.
While gene modification methods already exist – such as editing technology Crispr, which “snips” out the genes responsible for certain diseases, most of what is already out there involves permanently altering DNA. The difference with the new mRNA technology is that its effect is transient, and this, according to Mortazavi, can provide significant advantages.
“There are lots of technologies coming out that alter genes, but the difference with this is that it alters gene expression, rather than the genes themselves. Unlike Crispr, our target is at the RNA level, which means you don't have the risk of permanency,” he said. “In terms of safety, I think temporary has lots of benefits.”
For not only does it remove the risk of deleting a gene crucial for expression of other characteristics – it also is easy and quick to perform: “We can make our drug within a delivery system extremely quickly – RNA can be developed against any gene in three months for £30,000. So we are trying to take drug development from something which is slow to very fast.”
Silence Therapeutics is one of only a handful of pharmaceutical companies working on RNA-based therapeutics, and is the only one in the UK already conducting human trials – it expects to have some of its results ready for efficiency review during the second quarter of this year.
“We are one of a few companies worldwide who can modulate gene expression in this way, and critically, we have scaled up our technology for use in humans.”
Silence Therapeutics is publicly listed, but private companies have already started investing huge amounts in it – the US firm Moderna has spent $450m (£291m) in the field so far.
The reason why these companies are now able to carry out this technique, according the Mortazavi, is that there is now the human sequencing data available, and it all started with the completion of the Human Genome Project in 2003: “The Human Genome Project was the beginning of the genetic revolution. That revolution is now gaining rapid pace with the potential for a consumer product which can sequence an entire human genome for less than $1,000 (£648). The resulting new validated genetic targets will be an invaluable source of information for our genetic toolkit.”