Gene therapy thwarts hepatitis C in mice. (Infectious Diseases).

Gene therapy that induces infected liver cells to self-destruct slows hepatitis C dramatically in mice, scientists report.

Christopher D. Richardson of the Ontario Cancer Institute in Toronto and his colleagues implanted human liver cells into mice and infected the animals with the hepatitis C virus. The researchers then gave the mice three injections. Some got a self-destruct gene housed in an adenovirus that shuttles the gene into liver cells. Others received adenovirus without the therapeutic gene.

Five of six animals getting the gene therapy showed decreased amounts of hepatitis C virus in the infected tissue. Two appeared to clear the virus completely, Richardson and his colleagues report in the May Nature Biotechnology. Mice that didn't get the gene ended up with severe damage in the transplanted liver tissue.

The therapeutic gene encodes a protein called BH3-interacting domain death agonist precursor (BID). This protein can trigger cell suicide, but only when cleaved by a type of enzyme not normally present in people or mice. The researchers modified the BID gene so that its protein is recognizable to an enzyme made specifically in cells infected with hepatitis C virus. In that way, only these cells cleave the BID protein and unleash a suicide signal.

The therapy works by killing infected cells before they can send out legions of hepatitis C viral particles to infect other cells, says Richardson. The signal doesn't appear to affect nearby healthy liver cells, he says.

The therapy may expose "an Achilles' heel of the virus," Richardson says. The researchers are now looking at ways other than an adenovirus to deliver the modified BID gene.--N.S.