Human genome research is very much in the news these days following the publication of the complete genetic blueprint for human life. An Irish firm is making use of genome data in an effort to locate genes involved in disease.
HiberGen was incorporated in 1999 as a start-up biotechnology company and has been up and running since last year. It uses very advanced technology to scan chunks of the genome in a targeted search for genes associated with disease. It also searches for gene combinations that will tell how well a person might respond to a given drug therapy.
The patented technology is known as SNaPIT, pronounced "snap it", which is a good description of how it works.
Special enzymes are used to break up sections of DNA into small pieces and these are then analysed.
"We are a spin-out from University College Cork," explained Dr Maurice Treacy, chief executive of HiberGen. "The whole idea of the company came out of SNaPIT. That was patented at UCC in 1995."
Based in the Bray IDA Business Park, the company employs eight people, all of them involved in research, headed by chief scientific officer, Dr Pat Vaughan. There are three other PhDs and the rest of the team are either Masters or Bachelors of Science. If you phone HiberGen you are guaranteed to be answered by a technical specialist, if not the chief executive himself.
The technology was developed at UCC by Dr Vaughan and Prof Tommy McCarthy, the head of biochemistry. The work was co-funded by BioResearch Ireland and the two bodies hold the patents on SNaPIT, with HiberGen licensing access to the technology.
"It was about that time that I met Pat and we discussed if we could spin out a company," Dr Treacy said. He was then in the US working with the Genetics Institute in Boston, but came back to get HiberGen under way.
SNaPIT is based on the use of a special enzyme, a protein that can chop up DNA in a very specific way. "It is a cleavage technology," Dr Treacy explained. "What the technology does and why it is so good is it relies on the enzyme which is part of the patent."
DNA forms a single chain about 10 billion steps long. Dotted along it are the 30,000 to 40,000 genes that produce proteins, chemicals needed to sustain life.
Genes may sometimes carry small changes, mutations that can cause disease. These "single nucleotide polymorphisms" are what the SNaPIT technology is designed to search for, hence its full name, "Single Nucleotide Polymorphism Identification Technology".
If HiberGen believes it has found a gene associated with a disease, it uses SNaPIT to chop up the gene's DNA segment and then amplifies the fragments. It then delivers a "fragment analysis", Dr Treacy explained. "It looks at the different fragments and tells you if there is a difference between them."
The enzyme technology is matched by substantial computer power, which carries out the analysis of the data returned by SNaPIT. It can sort out hundreds of samples at a time. "The numbers are really important. It is a statistical analysis. You collect all the data and then you do your statistical analysis."
What they look for is differences between normal genes and potentially abnormal genes. "We try to find the gene variation that provides a strong link to the disease," Dr Treacy said.
The system works because the DNA analysis is done very quickly.
"We can do 10,000 genotypes a day," Dr Treacy said, with the system looking at up to 200 target genes at a time. A "snip" can be read in about eight seconds. "Huge computer power is absolutely necessary."
HiberGen uses the data in two distinct research areas, he explained. One is disease identification, making the connections between individual genes and diseases. The other is known as "pharmacogenomics", which involves trying to predict how well a drug might work in a particular patient on the basis of his genetic make-up.
The company is searching for genes related to a number of medical conditions such as preeclampsia and miscarriage, diabetes, advanced hardening of the arteries, kidney disorders, depression, Crohn's disease, heart disease and many others.
A disease of particular interest is diabetic nephropathy - damage to kidney tissues caused by diabetes. It affects between 35 per cent and 40 per cent of all diabetics and HiberGen hopes to identify the genetic profile of patients most at risk.
"The problem is they don't know which patients are going to go into nephropathy. We have found candidate genes that are implicated and we are now analysing them," Dr Treacy said.
Pharmacogenomics is an important area that could become a major earner for the company, he said. It will help to identify how a person with a given genetic profile might respond to a particular drug. Current drug design is based on a "one drug fits all" approach, even though many drugs are not well tolerated by all patients.
By knowing in advance how a person might respond, doctors will be able to tailor the drug treatments, ensuring that the best possible therapy is given. Regulatory agencies such as the FDA in the US and EMEA in Europe are beginning to demand some pharmacogenomic information on new drug products, opening up an opportunity for the company.
"The knowledge we generate will be used to develop new drugs," Dr Treacy said.
