Scientists Overcome Obstacle In Gene Therapy For Cystic Fibrosis, UK

Main Category: Cystic Fibrosis
Article Date: 27 Apr 2008 - 18:00 PDT

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Scientists from the UK CF Gene Therapy Consortium funded by the Cystic Fibrosis Trust have overcome a major obstacle in their ground-breaking gene therapy programme for Cystic Fibrosis.

Cystic Fibrosis (CF) is the UK's most common life-threatening inherited disease and is caused by a single defective gene. As a result, the internal organs, especially the lungs and digestive system, become clogged with thick sticky mucus resulting in chronic infections and inflammation in the lungs and difficulty digesting food.

Gene therapy to the lungs of those with CF involves delivering a healthy copy of the faulty CF gene to the cells lining the lung. The healthy gene is contained within a small circle of DNA called a plasmid. If enough plasmid can be delivered to the target cells in the lung, it may help correct the fault in the lung, which leads to 90% of deaths in Cystic Fibrosis.

Consortium members Drs Hyde and Gill, based at Oxford University, have developed a new version of the plasmid carrying the healthy CF gene. Previous research using an earlier version of the plasmid produced a mild flu-like effect in recipients. The team worked out this was probably due to the plasmids containing markers, known as CpG motifs which the body recognises as 'danger signals' triggering an inflammatory response in the lung. Drs Hyde and Gill have now removed all of the CpG motifs that cause this reaction. It is believed that this will lead to more of the healthy gene working in the lungs of people with Cystic Fibrosis and thus give greater therapeutic benefit.

Dr Gill said: "The new plasmid carrying the healthy CF gene is entirely free of CpGs, which we hope will reduce side-effects and improve the performance of the plasmid in the lung. Now we want to test the new plasmid in the clinic as part of the CF Gene Therapy Consortium's clinical programme commencing in 2008."

The research paper, entitled CpG-Free Plasmids Confer Reduced Inflammation and Sustained Pulmonary Gene Expression, will be published by Nature Biotechnology online at 6pm on 27 April. Go to http://www.nature.com/nbt

The Cystic Fibrosis Trust is the main funder of the UK CF Gene Therapy Consortium.

The Cystic Fibrosis Trust is the UK's only national charity dealing with all aspects of Cystic Fibrosis (CF). It funds research to treat and cure CF and aims to ensure appropriate clinical care and support for people with Cystic Fibrosis.

Cystic Fibrosis (CF) is the UK's most common life-threatening inherited disease. Cystic Fibrosis is caused by a single defective gene. As a result, the internal organs, especially the lungs and digestive system, become clogged with thick sticky mucus resulting in chronic infections and inflammation in the lungs and difficulty digesting food. Each week five babies are born with Cystic Fibrosis and three young people die - 90% from lung damage. Average life expectancy is just 31, although improvements in treatments mean a baby born today is expected to live longer.

In the early part of this decade, the Cystic Fibrosis Trust brought together the UK's leading CF gene therapy teams into a single working group - the UK CF Gene Therapy Consortium. There are now over 80 scientists and clinicians in Edinburgh, London and Oxford dedicated to a single research programme aimed at developing an effective gene therapy for CF lung disease

The Cystic Fibrosis Trust