Episome vectors offer fresh angle to gene therapy

Dec 6 2004

A European research team is seeking to overcome the early setbacks suffered by the promising new field of ‘gene therapy’ by developing a revolutionary delivery technique, known as ‘episome vectors’. This breakthrough could pave the way to treating hereditary diseases by injecting the body with healthy versions of damaged genes.

Many human diseases can be passed down from one generation of a family to the next. These hereditary diseases are, so to speak, written in the genes. Genes are segments of our DNA – the so-called ‘king of molecules’ – which give our cells instructions on how to produce proteins, the sophisticated molecules that build and maintain our bodies. Errors in their coding, known as mutations, can lead to the development of diseases, including Alzheimer’s and Parkinson’s.

As our understanding of genetics grew, many scientists and doctors became convinced that these genetic errors could be corrected through the introduction of properly functioning healthy genes. This field, known as ‘gene therapy’, was hailed as the way forward during much of the 1990s.

Then tragedy struck. When bioscientists and medical professionals first attempted to treat people with hereditary defects by implanting functional versions of damaged genes, several of the patients contracted cancer and died.

The EU-backed Epi-Vector team believe they have cracked the mystery behind these early deaths: the repair genes were transported to the required spot in the body on the back of disabled viruses that acted as delivery ‘vectors’.

“Certain viruses that were rendered harmless were used,” explains Professor Jürgen Bode of the Research Centre for Biotechnology in Braunschweig (GBF), a member of the Epi-Vector programme. “This was essentially a sensible approach because viruses inject their own DNA into the cells they attack... Then, they let themselves be reproduced by our own cells.”

The downside, he points out, is that we have no control over the location where this occurs on our chromosomes. If a virus invades a key genetic region of a cell, it can severely inhibit its functioning. In the worst-case scenario, this can lead to the breakdown and loss of genes which, in turn, can result in cancer.

This makes delivering genes on the back of even harmless viruses a little like playing genetic Russian roulette. The Epi-Vector consortium believes it has found a much safer alternative delivery mechanism. They are focusing on a new type of vector called an episome.

“Episomes are DNA elements that do not combine themselves with the genetic substance of the host DNA. Instead, they become anchored in a reversible manner only to certain support molecules in the nucleus of the cell – the same molecules used for stabilisation by human DNA,” the team explains.

The Human Genome Project – a huge international undertaking to compile the ‘book of life’, containing information on the 3 billion or so individual DNA molecules that make up the human body – identified these ‘DNA anchors’.

The information contained within the episome is jointly read with that of the chromosome and, together, they multiply every time cell division occurs. The consortium now wants to find out if episomes are suitable for a gentler form of gene therapy.

Professor Bode cautions that quick successes are unlikely. “Even if this method functions, considerable groundwork would still be required before the process could be applied in the medical field.”