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Friday, 14 December, 2001, 14:24 GMT
Gene therapy hope for sickle cell disease
The sickle cell's distinctive shape, BBC
The sickle cell's distinctive shape
Scientists have been able to correct sickle cell disease in mice using gene therapy.

The American researchers who carried out the tests say there are several hurdles to be overcome before the therapy can be used in humans, but that it offers hope for the future.

The research, detailed in the journal Science, shows how the gene therapy counteracts the faulty gene that causes red blood cells to "sickle", or become deformed.

The treatment involves the "anti-sickling" variant being delivered into bone marrow; it then incorporates itself into the stem cells that give rise to red blood cells.

'Sticky' cells

Sickle cell anaemia is an inherited blood disorder, which largely affects Afro-Caribbean and Asian patients, named after the distinctive shape formed by red blood cells.

The shape is affected because a protein within the cells - haemoglobin which carries oxygen from the lungs to the rest of the body - is different to normal.

It's a significant breakthrough in mice, but it's a long way from tying that to humans

Dr Phil Darbyshire, Birmingham Children's Hospital
Sickled cells stick together and link into long fibres, which means they cannot get through small blood vessels as easily as healthy cells.

This can stop oxygen getting through, and cause damage to organs, or, in some cases, strokes.

Dr Philip Leboulch, the lead researcher from Harvard Medical School and Massachusetts Institute of Technology, carried out tests in mice.

The mice had their bone marrow killed off with irradiation, and the altered gene delivered into their blood-forming stem cells.

Two different experiments saw an eight-fold reduction in sickle cells in one, and a complete eradication in the other.

Ten months later, all mice had the new genetic information in up to 99% of their red blood cells.

The new gene was able to prevent sickling and other signs of the disease.

Dr Leboulch said that although much more work needed to be done before the therapy could be used in humans, it was clear the treatment could be "highly efficient".

Hard to treat

Scientists have found it difficult to develop a gene therapy for sickle cell, which would be strong enough to counteract the body's genetic messages.

The problem is producing a whole "replacement" gene to counteract the faulty one, and getting it into the genome, or set of genes.

Dr Leboulch said: "It was difficult to transduce (transfer genetic material) an anti-sickling gene to bone marrow because it is so large, and then the expression level of this gene was very low and often 'silenced' once it entered bone marrow stem cells."

The scientists got around this by designing an "anti-sickling" gene, then using a retroviral vector, or a "coat" for the cell which used some DNA from the HIV-1 virus.

The DNA had previously been shown to be an effective delivery mechanism, and to improve the delivery of the altered cells genetic coded information.


Dr Leboulch said: "Usually when a copy of a new gene lands in the genome this way, it is very strongly influenced by its surroundings, and often gets silenced."

But he said when the expression level of the new genetic information was very high and was spread evenly throughout the cells, as in this case, "the gene can do its work".

For the therapy to work in humans, refinements need to be made to the process, scientists say.

Dr Phil Darbyshire, a paediatric haematologist at Birmingham's Children's Hospital, UK, said: "This looks very exciting. It's a significant breakthrough in mice, but it's a long way from tying that to humans."

See also:

07 Nov 01 | Health
New hope for sickle cell patients
17 Jun 01 | Health
Sickle cell transplant hope
23 Nov 00 | Health
GP tackles sickle cell anaemia
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