A More Careful Virus

Most gene-therapy trials use viruses to deliver genes to a patient’s cells, and most of those viruses are retroviruses, which have the ability to neatly splice their genes--and the human gene they’re carrying-- into a cell’s chromosomes. Although the viruses are crippled so that they can’t reproduce, they can still cause problems. Retroviruses are promiscuous, explains molecular geneticist Suzanne Sandmeyer of the University of California at Irvine. They can insert in the middle of a gene, knocking out the structural sequence for a protein. In their quest for a safer retrovirus, Sandmeyer and her colleagues are studying retrotransposons: bits of a cell’s own DNA that, like retroviruses, can copy and slot themselves into other sites in the cell’s genome. A yeast retrotransposon called Ty3, the researchers have found, is especially judicious: it always inserts itself in safe places, outside genes rather than inside them, and only near genes of which a yeast cell has many copies. Somehow, says Sandmeyer, it may be possible to confer that selectivity on a retrovirus that is being used to ferry a healthy human gene into a patient’s cells. One approach might be to insert into the virus the proteins coded for by Ty3, which the researchers have found are crucial in guiding Ty3 itself to the right spot.