| The prospects for treating
cystic fibrosis by gene therapy are looking brighter following successful tests
with a safer type of "shuttle"(短程梭运输工具)for ferrying(运送) replacement genes into a
patient's lungs. During the tests, a British-led research team inserted healthy
copies of the cystic fibrosis(囊性纤维变性) gene into cells lining sufferers' noses
with the aid of microscopic droplets(水滴,飞沫) of fat called liposomes Other groups that have attempted to correct the genetic defect that causes cystic fibrosis have used viruses as "vectors" (媒介) to carry the healthy gene into target cells. Unfortunately, viruses can also cause inflammation in the lungs, an undesirable side effect in CF patients, whose lungs are already diseased. The new method for introducing corrective genes into the lungs of CF patients promises to be much safer. Cystic fibrosis is caused by defects in a gene called CFTR, which plays a part in the transport of chloride ions(离子) out of the cells lining the lungs, airways and gut. Defects in this gene mean that patients have difficulty expelling mucus(黏液) and inhaled (吸入) microorganisms from their lungs. As a result, they are very susceptible to lung infections, and usually die at around 30 years old. As an alternative to the viral vector, the researchers, linked loops (环)of DNA containing healthy copied of the CFTR gene to microscopic liposomes. When the liposomes come in contact with a cell, they fuse(融合) with its outer membrane, and release the DNA into the cell's interior. To test the system, the team sprayed the liposomes into the noses of volunteers with cystic fibrosis. "The cells lining the nose are very similar to those lining the lung," explains David Porteous of the human genetics group in Edinburgh. But the ceils in the nose are easier to monitor, and the risks are lower if any nasal (鼻的)cells are damaged. In the event(结果,到头来), none of the volunteers suffered any unpleasant side effects. And a single spraying partially corrected the cystic fibrosis defect. The researchers assessed the effectiveness of the treatment by measuring the voltage(电压,伏特) across the layer of cells lining the nose. This voltage is higher in cystic fibrosis sufferers than in healthy people. A single spraying reduced this difference by around 20 per cent. The re-searchers reported that the effect lasted for up to a week. The British researchers have yet to test their spray in the lungs, but are confident that the liposomes will not cause inflammation. The question, however, is how effective the shuttle system is. In the nose, the researchers had to add more copies of the healthy CFTR gene to match the performance of the adenovirus. This is because adenoviruses carry genes directly to the cell' s nucleus, ensuring that the instructions they carry are read. Genes carried by liposomes are only guaranteed a ride into the cell's cytoplasm, and fewer will find their way to the nucleus. Many will be broken down by the cell's waste disposal system before they get there. Bob Williamson, who heads the group at St. Mary's Hospital, says this will require much more efficient vectors. "People in 10 to 15 years will laugh at the crudity of the liposomes and viruses that we're using today, " he says. The aim is to make customized vectors which combine the best aspects of both systems, and include other genetic sequences to ensure that the information carried by the healthy CFTR gene is used by the target cells lining the lungs. |