Once HIV conquers a human cell, it
will stay there forever.
It inserts its deadly genome
permanently into its victims' DNA, forcing them to require medical treatment
for the rest of their life.
But now, for the first time,
researchers in Philadelphia have found a way to completely delete HIV from
human cells by ‘snipping’ them out.
The team of Temple University School
of Medicine said the breakthrough marks the first successful attempt to
eliminate latent HIV-1 virus from human cells – and could be a cure for other
latent infections.
‘This is one important step on the
path toward a permanent cure for AIDS,' said Kamel Khalili, PhD, Professor and
Chair of the Department of Neuroscience at Temple.
'It's an exciting discovery, but
it's not yet ready to go into the clinic. It's a proof of concept that we're
moving in the right direction,' he added.
In a study published by the
Proceedings of the National Academy of Sciences, Dr Khalili and colleagues
detail how they created molecular tools to delete the HIV-1 proviral DNA.
When deployed, a combination of a DNA-snipping enzyme called a nuclease and a targeting strand of RNA called a guide RNA (gRNA) hunt down the viral genome and remove the HIV-1 DNA.
From there, the cell's gene repair
machinery takes over, soldering the loose ends of the genome back together – resulting
in virus-free cells.
'Since HIV-1 is never cleared by the
immune system, removal of the virus is required in order to cure the disease,'
explained Dr Khalili.
These molecular tools also hold
promise as a therapeutic vaccine; cells armed with the nuclease-RNA combination
proved impervious to HIV infection.
Worldwide, more than 33 million
people have HIV, including more than 1 million in the United States.
Every year, another 50,000 Americans
contract the virus, according to the U.S. Centers for Disease Control and
Prevention.
In the UK, around 100,000 people
were living with HIV in the UK in 2013. That’s around one person in 665.
Although highly active
antiretroviral therapy (Haart) has controlled HIV-1 for infected people in the
developed world over the last 15 years, the virus can rage again with any
interruption in treatment.
'The low level replication of HIV-1 makes patients more likely to suffer from diseases usually associated with ageing,' Dr Khalili said.
These include cardiomyopathy – a
weakening of the heart muscle – bone disease, kidney disease, and
neurocognitive disorders.
'These problems are often
exacerbated by the toxic drugs that must be taken to control the virus,' Dr
Khalili added.
Researchers based the two-part HIV-1
editor on a system that evolved as a bacterial defence mechanism to protect
against infection.
Dr Khalili's lab engineered a
20-nucleotide strand of gRNA to target the HIV-1 DNA and paired it with a
DNA-sniping enzyme called Cas9 and used to edit the human genome.
'We are working on a number of
strategies so we can take the construct into preclinical studies,' Dr Khalili
said.
'We want to eradicate every single
copy of HIV-1 from the patient. That will cure AIDS. I think this technology is
the way we can do it.'
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