San Francisco
IT MAY sound like sheer madness, but American scientists say that
modified versions of HIV could ferry therapeutic genes into patients with
genetic disorders. They have already created a weakened form of HIV that can
deliver DNA into rats without causing disease.
Retroviruses, the group that includes HIV, are good vehicles for delivering
genes into cells because they infiltrate chromosomes with their genetic
material. The drawback is that most retroviruses cannot penetrate the nucleus
which contains the chromosomes, so they must wait for its membrane to dissolve
during cell division. 鈥淢any tissues we want to target鈥攍ike lung, muscle
and brain鈥攔arely divide,鈥� says Inder Verma, a gene therapy specialist at
the Salk Institute in La Jolla, California.
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In 1992, however, scientists discovered that HIV and its close relatives,
known as lentiviruses, can sneak through the nuclear membrane. Verma and his
colleagues at Salk and the Whitehead Institute for Biomedical Research in
Cambridge, Massachusetts, decided to make the most of this ability.
To create a safe vehicle for gene therapy, the researchers removed the genes
that HIV needs to produce new virus particles. But the virus could still leap
into chromosomes, because it had been made in the presence of a 鈥渉elper鈥� virus
that gave a dose of the enzymes HIV needs to infiltrate a chromosome. The helper
was altered so that it could not itself be packaged into infectious virus
particles.
The researchers injected the vector, containing a marker gene called
lacZ, into rats鈥� brains. Using antibodies against the protein made by
lacZ, they found that the introduced gene was still working a month after
the treatment. With a conventional retroviral vector, no protein was detected,
showing that the gene had not inserted into a chromosome (Science, vol
272, p 263).
Joseph Sodroski, an HIV researcher at the Dana-Farber Cancer Institute in
Boston, says the work is impressive, but adds that the real challenge will be to
convince the public that HIV can be a safe medical tool. Even though the
researchers have removed HIV鈥檚 deadly genes, there is a small chance the
crippled virus could acquire replacements from the helper.
Verma agrees that HIV鈥檚 reputation could overshadow the work, but sees a
solution: the virus will be less risky if some genes on the helper virus come
from lentiviruses that cannot reproduce in human cells. He aims to make a helper
containing only 10 per cent HIV genes.