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Once HIV
invades the body, it doesn’t want to leave. Every strategy that
scientists have developed or are developing so far to fight the virus –
from powerful anti-HIV drugs to promising vaccines that target it –
suffers from the same weakness. None can ferret out every last virus in
the body, and HIV has a tendency to hide out, remaining inert for years,
until it flares up again to cause disease.
None, that
is, until now. Kamel Khalili, director of the Comprehensive NeuroAIDS
Center at Temple University School of Medicine, and his colleagues took
advantage of a new gene editing technique to splice the virus out of the
cells they infected – essentially returning them to their pre-infection
state. The strategy relies on detecting and binding HIV-related genetic
material, and therefore represents the first anti-HIV platform that
could find even the dormant virus sequestered in immune cells.
Even more
encouraging, they also used the system to arm healthy cells from getting
infected in the first place, by building genetic blockades that bounced
off HIV’s genetic material. “It’s what we call a sterilizing cure,”
says Khalili.
His work was
done on human cells infected with HIV in cell culture, but, he believes
the results are robust enough to move into animal trials and eventually
into testing the idea in human patients.
The key to
the strategy is the gene editing technique known as CRISPR, a way of
precisely cutting DNA at pre-specified locations. CRISPR acts as a
customizable pair of molecular scissors that can be programmed to find
certain sequences of DNA and then, using an enzyme, make cuts at those
locations. Because HIV is a retrovirus, its genetic material comes in
the form of RNA; the virus co-opts a host cell’s genetic machinery to
transform that RNA into DNA, which it then inserts into the cell’s
genome. HIV’s genes, which it needs to survive, then get churned out by
the cell.
Khalili
designed a CRISPR that recognized the beginning and end of HIV’s DNA
contribution, and then watched as the enzyme snipped out HIV from the
cell’s genome. “I’ve been working with HIV almost since day 1 [of the
epidemic] and we have developed a number of molecules that can suppress
transcription or diminish replication of the virus. But I have never
seen this level or eradication,” he says. “When you remove the viral
genes from the chromosomes, basically you convert the cells to their
pre-infection state.”
The
advantage of the system lies in the fact that CRISPR can recognize viral
genes wherever they are – in infected cells that are actively dividing,
and in infected cells in which the virus is dormant. Current drug-based
strategies can only target cells that are actively dividing and
releasing more HIV, which is why they often lead to periods of
undetectable virus but then cause levels of HIV to rise again. That’s
the case with the Mississippi baby, who was born HIV positive and given
powerful anti-HIV drugs hours after birth and appeared to be
functionally cured of HIV when the virus couldn’t be detected for nearly
four years, but then returned.
Khalili
admits that more work needs to be done to validate the strategy, and
ensure that it’s safe. But it’s the start, he says, of a potential
strategy for eradicating the virus from infected individuals. That may
involve excising the virus as well as bombarding it with anti-HIV drugs.
“We can get into cells, eradicate the viral genome, and that’s it,” he
says.
Culled from TIME
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