Researchers are making slow progress, but a team from the Salk Institute for Biological Studies in La Jolla, California, reported a promising new development on Thursday. They used a disabled version of HIV - a copy of the virus with all its disease-causing genes stripped out - to deliver human genes into the cells of mice, inducing them to generate human blood cells.

The introduced genes were those from human hematopoietic stem cells (HSCs). These are precursor cells in the bone marrow and other sites of blood production that specialise in generating different types of blood cell.

Researchers have had their eyes on HSCs as possible targets for gene therapy to treat inherited blood disorders such as sickle cell anaemia or acquired diseases like leukaemia.

Viable candidate

First, however, a suitable delivery system for installing the corrective genes must be found. In mice at least, HIV appears to be a viable candidate. After "infecting" the mice with the modified HIV, the scientists found evidence of cells produced by human stem cells in the blood of the animals.

Inder Verma, one of researchers working on the project, said they hoped to substitute the human genes that control production of two blood clotting proteins known as Factor VIII and Factor IX, which are often used to treat haemophilia.

Gene therapy has been slow to show positive results because it is difficult to get the desired new genes inserted into the correct position in cells so that they are expressed in the right place at the right time. Those successes which have been achieved have tended to be short-lived.

But in this experiment, the genes had been expressing for 22 weeks when the mice were killed for examination. "That is a quarter of the life of mice," Verma said. Between five and 15% of the cells in the mice tested positive for human genes.

Human trials

If the same level of production could be achieved in humans, that would be enough to treat haemophilia, Verma said. "It can definitely produce a therapeutic amount," he said. Further animal studies will be done before an application is made to do human trials.

Writing in the journal Science, the team looked ahead at the possibility of using HIV as a gene therapy "vector" in humans.

They said: "A potential problem for the application of HIV vectors to human studies is safety. In this regard, recent improvements, including self-inactivating vectors, packaging constructs eliminating all accessory genes, and inducible packaging cell lines, could further minimise the risk.

"The use of HIV vectors provides a previously unexplored basis for the study of hematopoiesis and for human gene therapy with the use of HSCs."

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