CSIRO's revolutionary "gene shears" technology has entered clinical trials in adults as the first step in developing a potential treatment for the human immunodeficiency virus (HIV) which causes AIDS, the chief executive of Gene Shears Pty Ltd, Dr Leigh Farrell announced today.
The Phase One clinical trial, conducted at St Vincent's Hospital, Sydney, is testing the safety and ability of Gene Shears' patented gene therapy to inhibit HIV replication in infected patients.
HIV attacks a special class of white blood cell, the CD4+ lymphocyte, which forms the backbone of the human immune defence against attacks by infection. Loss of these white blood cells causes the immune system eventually to break down.
The basis for the trial is the original discovery by CSIRO Plant Industry molecular biologists Dr Jim Haseloff and Dr Wayne Gerlach that naturally-occurring enzymes called ribozymes (dubbed "gene shears") can be used selectively to chop up pieces of genetic material. Gene Shears Pty Ltd went on to prove in laboratory experiments that ribozymesit could be used to prevent the replication of HIV by cutting its genetic material.
The chief executive of CSIRO, Dr Malcolm McIntosh, welcomed news that human trials of the anti-HIV gene shears were under way. "It is extremely pleasing that this fundamental Australian discovery is now starting to bear fruit in the form of practical applications which promise to improve human health and wellbeing," he said.
"It highlights the national importance of CSIRO continuing to perform excellent basic science designed to gain new knowledge."
The Sydney experiment involves six pairs of identical twins, of whom one of each pair is HIV-positive.
CD4+ white blood cells taken from the uninfected twin are equipped with the anti-HIV ribozyme and then infused into the HIV-infected twin.
The trial seeks first to establish that the ribozyme is safe and has no side-effects on the patients, and secondly to find out how long the CD4+ cells protected by the anti-HIV ribozyme survive in the body.
The research team hopes that the Gene Shears ribozyme will not only protect white blood cells equipped with it, but will also prevent more HIV being produced by infected cells before it can invade healthy cells.
The clinical trial uses a harmless virus as a "taxi" to insert the ribozyme into the target CD4+ cells. The ribozyme acts by slicing up the messenger RNA which instructs the HIV-infected cell how to make new infectious HIV particles.
The hammerhead ribozyme technology was originally patented by CSIRO in 1987. Gene Shears Pty Limited was established the following year by CSIRO and the French seed firm Groupe Limagrain Pacific Pty Ltd, the Australian subsidiary of one of the world's largest seed companies, Groupe Limagrain, to commercialise the technology. In 1991 the partners were joined by Johnson & Johnson Pty Ltd, the Australian subsidiary of US healthcare giant Johnson & Johnson.
Over the next three years the Gene Shears licensees plan to test the ribozyme gene therapy against a range of other human diseases.
Research is also well-advanced into uses of ribozymes in the agricultural and food industries. For example, a range of virus-resistant vegetable crops developed with gene Shears' ribozymes will undergo field trials in 1997/98.
And by 2000, Gene Shears and Groupe Limagrain hope to market the world's first tomato seeds created using male-sterile tomato lines with the gene shears technology.