杏吧原创

STEALTH viruses could be used to sneak past the immune system and deliver
missing genes to people with disorders such as cystic fibrosis.

Maria Croyle and her colleagues at the universities of Pennsylvania and Texas
鈥渄isguised鈥� adenoviruses by adding the polymer polyethylene glycol (PEG) to
proteins on their coats. When these disguised viruses were used to deliver genes
to the lungs of mice, the new genes kept working for much longer: 42 days
instead of just 4.

The trick of adding PEG to proteins to hide them from the immune system has
long been used by the drugs industry. But Catherine O鈥橰iordan and her colleagues
at the biotech company Genzyme were the first to try it on viruses.

鈥淭he trouble with using adenoviruses for gene therapy is that most people
have antibodies to these viruses already,鈥� O鈥橰iordan says. Two years ago, her
team showed that 鈥淧EGylating鈥� adenoviruses protects them from antibodies.

Antibodies are not the only problem. The cells to which genes are delivered
often express not only the desired gene but also any viral genes remaining in
the adenovirus. That makes them targets for the body鈥檚 killer T cells. Now
Croyle鈥檚 team, which has developed a faster method of PEGylating viruses, has
shown that the technique can prevent the destruction of the recipient cells.
鈥淧EGylation may interfere with the processing of viral proteins by the immune
system,鈥� Croyle says.

Using gene therapy to treat people with cystic fibrosis has proved more
difficult than expected. 鈥淭he results have not been spectacular,鈥� says Croyle.
Now she and O鈥橰iordan hope to carry out trials of stealth viruses in people. But
sneaking past the immune system is just part of the challenge, they say. The
genes also have to be delivered to the right cells, and must be expressed
permanently, not just for days or weeks.