To correct these problems, Sadelain and colleagues made two changes to the standard technique. First, instead of using an oncovirus to ferry the -globin gene into the target cells, they used a version of HIV stripped of most of its genes. This was preferable because HIV usually delivers intact sequences, whereas oncovirus-mediated genes are prone to rearrangement. Sadelain and colleagues reasoned that longer LCR sequences would give the target cells more control over gene expression and reduce variability in protein production. After infecting mouse bone marrow cells with altered virus, the researchers transplanted the cells into mice with -thalassemia or whose bone marrow had been destroyed with radiation.
Safety remains the big hurdle for the technique.
Although animal trials are reassuring, Sadelain expects extra scrutiny in the move to humans.