Scientists are one step closer to creating a drug that could prevent HIV infection and even remove all the dormant copies of the deadly virus from patients with the more advanced disease.
Researchers at Salk Institute for Biological Studies in
the US said such a drug could become a reality by customising a powerful
defense system used by many bacteria and training this scissor-like
machinery to recognise the HIV virus.
When a copy of the HIV virus sneaks into a human cell, it co-opts the
cell's own molecular machinery to make copies of the virus's genetic
material and then buries these copies in the cell's own genes.
From there, the host's cell becomes an HIV factory, making new copies of the virus to spread throughout the body.
Existing HIV drugs target individual steps of this lifecycle; some
stop the virus from integrating into cells' DNA, for instance, while
others try to stop the affected cells from producing more virus.
Hsin-Kai Liao, first author of the study and a research associate in
the lab of Juan Carlos Izpisua Belmonte, a professor of Salk's Gene
Expression Laboratory and senior author of the study, said the problem
with these drugs is that they don't actually remove the copies of the
virus that are hidden within cells' DNA.
These copies can remain dormant for years and then activate again.
Liao and Belmonte turned to a molecular defense system called CRISPR that bacteria use to cut up foreign DNA at specified spots.
Liao and Belmonte were intrigued by its defensive ability and
wondered if CRISPR could be programmed to slice and destroy viruses
inside human cells.
CRISPR uses bits of genetic material called guide RNAs to dictate its
cuts, so the scientists developed guide RNAs that bind to unique spots
on the HIV virus.
They added CRISPR, the guide RNAs and other molecules needed for the
system to work to immune cells that had been infected with HIV, and
found that CRISPR successfully cut the right spots in HIV's genes,
inactivating the virus.
This resulted in the virus being completely removed from up to 72 per
cent of cells. CRISPR chopped up loose copies of the virus as they
initially infected the cell and also cut up HIV that was hidden and
dormant within the cells' DNA.
The Salk team also illustrated in a more complete way how CRISPR
targets HIV in living human cells, verifying that it works both before
and after the virus is embedded in the genome.
Researchers also added the CRISPR system to human cells before they
became infected with HIV. Having the system in place prevented an
infection - CRISPR chopped up any copies of the virus before they could
start replicating.
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