91av

SLICING one virus’s DNA in half vastly improves its ability to shuttle genes
into cells, researchers in North Carolina have discovered.

Adeno-associated virus (AAV) has fewer toxic effects than many other viruses,
and the genes it carries can remain active in cells for months or even years.
There’s just one problem. “For some applications it just isn’t fast enough,”
says Jude Samulski of the University of North Carolina, Chapel Hill. It can take
weeks for the genes carried by AAV to be switched on in the target cells.

Samulski and his UNC colleague Doug McCarthy suspected AAV might be slow out
of the starting gate because it contains only single-stranded DNA. After
replication, the virus discards the other strand because only one will fit
inside its protein coat. This means that before gene expression can begin in
target cells, the other strand must be shuttled in by another virus, or enzymes
must recreate the missing DNA.

Now McCarthy and Samulski have shown that if the length of the virus’s DNA is
reduced by half, the remaining DNA can slip into the viral coat without one
strand having to be discarded.

This lean, mean microbe is much more efficient. While it takes about 500
ordinary AAV particles per cell to switch on genes in cells grown in culture,
just five mini-AAVs can do the same job. And in mice, the reduced virus turned
on genes in a few days instead of the few weeks it takes the normal virus.

There is one drawback, however. The streamlined virus can only hold genes
about 2500 DNA-letters long. That’s too small to carry larger human genes, but
Samulski says its efficiency still makes it attractive for many applications.
“We are thinking about small anti-cancer proteins, for example,” he says. “It
could be really great for that.”