- The Observer, Sunday April 22 2001
Researchers say HIV's almost perfect ability to evade immune defences makes it ideal for carrying new genes into patients' bodies.
Now scientists at the Salk Institute in California, one of the world's leading biology research centres, have created a special 'harmless' strain of HIV and have begun negotiations with the US Food and Drug Administration (FDA) to begin clinical gene therapy trials this year.
'The first trials will probably involve patients suffering from inoperable cancers,' said the project leader, Professor Inder Verma of the institute's genetics laboratory. 'However, we expect our HIV technique will have far wider applications.'
The plan is extraordinarily controversial, however. HIV has caused more than 22 million deaths across the globe in the past two decades, and has become one of mankind's most feared viruses. The idea that even a genetically doctored version of such a deadly entity should be deliberately injected into patients is likely to cause considerable unease.
'It is a startling idea,' Verma admitted. 'However, we have neutered the HIV by removing all six of its genes. These cause all its deadly effects, and so we can be absolutely sure infected patients will not be made ill.'
Many illnesses - including haemophilia, cystic fibrosis, and various cancers - are caused when a gene in a patient's body fails to work properly. In the past few years, breakthroughs in genetics have led gene therapy scientists to try to replace malfunctioning genes.
However, researchers have faced a major stumbling block: Finding a carrier, or vector, for transporting such a gene into a patient's body. Most efforts have concentrated on using viruses because they replicate by inserting themselves into a patient's own collection of genes. When a person's cells divide, so do their genes and so do those of the virus.
'All you have to do is splice a gene into a virus, infect a patient with it and you should be able to create countless copies of that missing gene,' said Verma.
At least, that is the idea. Unfortunately, trials based on this methodology have frequently come unstuck. In some cases, the genetically modified viruses would not replicate inside a patient.
In many others, it was discovered that patients' bodies would launch immune attacks on the genetically modified vector viruses, a problem highlighted by the case of 18-year-old American Jesse Gelsinger. He died last year after taking part in a gene therapy trial at the University of Pennsylvania, using a virus called an adenovirus that was genetically modified to treat liver disease.
Such adenoviruses will divide and replicate in the body, and have become popular as vectors in gene therapy research. However, they provoke an immune response that destroys them in two or three days - often before they can impart their genetic message to the targeted cells.
'That is fine if you want to tackle something quickly,' said Verma. 'However, as the virus is constantly being mopped up by patients' immune systems, you have to inject masses of them to have an effect. In the case of Jesse Gelsinger, doctors used too much and the pathogenic response killed the boy.'
However, the HIV virus is renowned for its ability to sidestep, and then destroy, the very immune defence cells that are supposed to protect our bodies. Hence its attraction to scientists.
Researchers have found that modified HIVs can now be made in sufficient amounts to avoid immune attacks for considerable periods. 'They are the best candidate vectors for gene therapy that we have come across,' said the professor.
Following the creation of their harmless strain of HIV, the Salk Institute has licensed the technology to Californian biotechnology company Cell Genesys, of which Verma is a director. This firm is now negotiating with the FDA about starting human trials.
'We expect approval this year and that trials will begin straight away,' he added. 'Ultimately, we want to infect young babies and cure them for life from diseases. It would be the perfect medical analogy of turning swords into ploughshares.'
