LONDON - The genomics explosion has produced a bottleneck in the development of gene therapy that will not be removed until efficient gene delivery systems are developed.

This is the view of Gareth Benyon, CEO of Neurovex Ltd., a UK start-up that is developing gene vectors based on the herpes simplex virus (HSV).

"There are hundreds of thousands of genes out there, and no means of delivering them, he told BioWorld International. "To date around 3,000 patients have been treated in 300 protocols. The technology is at a very early stage. The companies that crack the best delivery system for a particular tissue range will set the gold standard."

Neurovex was spun out of University College London in January 1998 by Robert Coffin, research director, and David Latchman of the Institute of Child Psychiatry in London.

In February 1998 it received #3 million (US$4.9 million) from the Merlin Group. Benyon, who joined the company in November from the post of European vice president for Amylin Pharmaceuticals, said the funding will last until the end of 2001.

Neurovex is developing the HSV vector for central nervous system diseases and single-gene inherited metabolic disorders.

"Over zillions of years HSV has evolved to exquisitely target the nervous system without sparking an immune response or killing neural cells," Benyon said. "So we are starting with a naturally adapted vector."

The company has filed for a number of patents on gene deletions that prevent HSV replicating in the host. It also harnessed part of the viral genome to drive long-term gene expression, which will be essential in treating chronic central nervous system diseases such as Parkinson's.

"We have overcome problems associated with other vectors, where you get initial gene expression which then peters out," he said. "In addition, HSV has a large carrying capacity, of around 70 kilobases, which is only exceeded by the pox virus."

In Parkinson's disease this high capacity will give Neurovex the means to deliver a cassette of genes designed to circumvent the damage and prevent further deterioration. For example, it could deliver neurotrophic factors together with enzymes such as tyrosine hydroxylase that may boost the activity of the remaining dopaminergic neurons.

The company also plans to develop the HSV vector for immunotherapy. The vector can infect and deliver genes at high efficiency to dendritic cells in the skin responsible for alerting the immune system to foreign antigens. They can also alert the immune system to antigens, such as those from tumors, to which it has become tolerized.

"Delivery of antigens to dendritic cells is not possible by other means and provides a promising platform, which as well as providing antitumor vaccines could also be used for vaccines for infectious diseases," Benyon said. "This is a very neat piece of technology. We have some unique advantages which will emerge as the patent filings become public."