A London-based company takes steps towards personalised medicine, without jumping on the RNAi bandwagon.
Andrea Chipman
Tailoring medicine to the specific genetic structure of a patient has long been the holy grail of medicine. London-based biopharmaceutical company ValiRx says it is a little closer to providing personalized cancer treatment, using innovative gene silencing technology.
ValiRx’s epigenetic platforms do two things: probe gene activity in a given tissue and shut that activity down. This offers a tool for both diagnostics and drug development. Unlike many companies in the gene-silencing arena, ValirX have eschewed RNA interference (RNAi) in favour of directly targeting the genome.
According to Chief Executive Satu Vainikka, “The diagnostics and drug programs are complementary. The diagnostics platform will map a cancer and say the cancer is because [certain] genes are activated, and then the drug development platform will be completely able to switch off those genes.”
ValiRx listed on London’s Alternative Investment Market last October, after forming in July 2006. It is a ‘virtual’ company, acquiring small start-ups in the process of developing therapeutic and diagnostic products. Their largest subsidiary is Cronos Therapeutics Ltd., of which they own a 61% stake.
Imperial spin-off
The key technology hinges on gene inactivation by chromatin engineering – or GeneICE. Chromatin is the densely packed genetic material at the heart of the cell. For genes to be expressed, the chromatin structure must be in an open conformation. So by controlling chromatin state at a local level, you can influence gene expression. Such a technique was pioneered by Professors Simak Ali and Laki Buluwela from Imperial College.
“The technology we originally described was designed to engineer a gene regulatory protein, known to be important in breast cancer, to shut down rather than promote the use of genes associated with tumour growth and survival,” says Ali.
The team used a fusion protein to specifically target the errant gene, and then block its expression. According to Ali, “Using our approach it may be possible to reprogram the genome of a cancer cell, such that groups of co-ordinately regulated deleterious genes are shut down”.
Imperial patented the GeneICE technology via Gene Expression Technologies Ltd, a spin-off that eventually became Cronos. The technology received its U.S. patent last month, after getting European patent approval in 2006.
ValiRx has further developed this technology, by designing small DNA–protein hybrid molecules to silence genes. The nucleic acid component targets an individual gene implicated in the disease mechanism. The polypeptide part then attracts histone deacetylase complex to the site. This enzyme causes a local condensing in chromatin, which represses expression of the gene.
Alternative to RNAi
Many companies working on gene silencing techniques exploit RNAi, whereby degradation of messenger RNA prevents protein synthesis. RNAi remains hot property. For example, last year, Merck acquired Sirna Therapeutics, a San Francisco biotech specialising in RNAi and gene silencing, for $1.1 billion.
Ali noted that RNAi is limited by the availability of efficient systems for administering genes in a therapeutic setting, and for achieving long-term responses. Because ValiRx targets the ‘first step of the biological cascade,’ or the genes themselves, the company hopes to produce more efficient treatments for many diseases, including cancer.
Eventually, ValiRx aims to market an integrated personalized medicine package for individual patients. The company raised £2 million in its initial public offering on AIM and also has a research collaboration agreement with Cancer Research Technology, the commercial arm of Cancer Research UK. It continues to look for acquisition opportunities.