Tripping up avian flu

DNA rings hinder virus reproduction in chicken embryos

Small rings of designer DNA can block bird flu virus from reproducing, a new study suggests.

The work is still preliminary, but researchers say that treating chickens with such DNA rings — either by injection or by an inhaled mist — might help to slow the spread of the virus. Eventually, the technique could protect people from the disease. Efforts to develop an effective vaccine for avian flu have been unsuccessful.

Though avian flu has not yet been found in the United States, the virus has infected 381 people worldwide and killed 240 of them, according to the World Health Organization.

Once in the cells, the DNA rings produce another kind of genetic code–carrying molecule called short interfering RNAs. The letters of genetic code in these siRNAs, as they’re called, exactly match part of a gene in the virus’s genome. So when the virus tries to replicate, the siRNAs can recognize and disable that viral gene, thus preventing the virus from reproducing.

“The findings … provide a basis for the development of small interfering RNAs as prophylaxis and therapy for avian influenza infection in birds and humans,” write Kai Zhou and his colleagues at the Chinese National Research Center for Wildlife Born Diseases in Beijing in a paper to appear in an upcoming Journal of Biotechnology.

“The approach is well worth pushing,” comments Herman Eisen, an MIT virologist who has performed similar research for other flu viruses. “The hold up is being able to deliver it. Like any kind of gene therapy, it’s very difficult.”

Zhou’s team built on previous work that used RNA interference to disrupt reproduction of other kinds of flu virus. In most of the earlier research, harmless adenoviruses instead of DNA rings carried the siRNAs into the animals’ cells. People’s immune systems can often destroy adenoviruses, which could defeat potential therapies. The DNA rings, called plasmids, avoid this problem and can be mass produced cheaply by using bacteria to churn out copies.

The researchers identified a part of the avian flu–virus genome that is nearly identical among the virus’s many mutant strains. By designing the plasmid to target that segment of genetic code, Zhou and his colleagues hoped to ensure that the plasmid would work against the many variants of avian flu.

As it turned out, that region of the virus’s genome contains code for a crucial protein. This protein plays two roles for the virus: providing an encapsulating coating when the virus packs up to move to a new cell and enabling the production of proteins by the virus’s other genes. By knocking out production of that key protein, the team’s plasmid reduced proliferation of the virus in chicken embryos by up to 70 percent. Using plasmids could simplify delivery because unlike the adenoviruses often used to deliver gene-based therapies, the plasmid does not insert any DNA into the animals’ own chromosomes, a process that is prone to dangerous errors.

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