gene editing iStock.com/Artem_Egorov
CRISPR-Cas gene editing eliminates HIV in lab
New research presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024), held in Barcelona from 27–30 April, shows how the latest CRISPR-Cas gene editing technology can be used to eliminate all traces of HIV from infected cells in the laboratory. The studies, conducted at Amsterdam University Medical Center (Amsterdam UMC), present a significant breakthrough in the search for a cure for HIV.
C
The scientists deployed CRISPR-Cas
successful, enhancing its delivery to HIV-infected
molecular scissors and two gRNAs against
cells. Moreover, they were able to target ‘hidden’
RISPR-Cas gene editing technology
‘conserved’ HIV sequences, meaning they focused
HIV reservoir cells by focusing on specific
is a groundbreaking technique that allows for
on parts of the virus genome that stay the same
proteins found on the surfaces of these cells
precise alterations to the genomes of living
across all known HIV strains, and achieved cure
(CD4+ and CD32a+).
organisms, enabling scientists to accurately target
of HIV-infected T cells. By focusing on these
“We have developed an efficient combinatorial
and modify specific segments of an organism’s
conserved sections, the approach aims to provide
CRISPR-attack on the HIV virus in various
DNA. Functioning like molecular ‘scissors’ with
a broad-spectrum therapy capable of combating
cells and the locations where it can be hidden in
the guidance of guide RNA (gRNA), CRISPR-
multiple HIV variants effectively.
reservoirs, and demonstrated that therapeutics can
Cas can cut the DNA at designated spots. This
However, the team found that the size of the
be specifically delivered to the cells of interest,” the
action facilitates either the deletion of unwanted
vehicle or ‘vector’ used to transport the cassette
scientists stated. They said their findings represent
genes or the introduction of new genetic material
encoding the therapeutic CRISPR-Cas reagents
a pivotal advancement towards designing a cure
into an organism’s cells, paving the way for
into the cells presented logistical challenges,
strategy for HIV, while acknowledging that their
advanced therapies.
as it was too large. Thus, they trialled various
work at this stage is only a proof of concept.
One of the significant challenges in HIV
techniques to reduce the size of the cassette — and
“Our next steps involve optimising the
treatment is the virus’s ability to integrate its
therefore the vector system itself. In simpler terms,
delivery route to target the majority of the HIV
genome into the host’s DNA, making it extremely
they’re attempting to pack oversized luggage
reservoir cells,” the researchers said. “We will
difficult to eliminate. Numerous potent antiviral
into a compact car for a journey to the infected
combine the CRISPR therapeutics and receptor-
drugs are currently in use for treating HIV
cell, leading them to find ways to downsize the
targeting reagents and move to preclinical
infection — but despite their efficacy, lifelong
‘luggage’ (cassette) for easier transport. Another
models to study in detail the efficacy and safety
antiviral therapy is essential, as HIV can rebound
issue they wanted to overcome was reaching the
aspects of a combined cure strategy. This will be
from established reservoirs when treatment is
HIV reservoir cells that ‘rebound’ when HIV
instrumental to achieving preferential CRISPR-
halted. CRISPR-Cas genome editing thus provides
antiretroviral treatment is stopped.
Cas delivery to the reservoir cells and avoiding
The researchers further evaluated various
delivery into non-reservoir cells. This strategy
“Our aim is to develop a robust and safe
CRISPR-Cas systems from different bacteria
is to make this system as safe as possible for
combinatorial CRISPR-Cas regimen, striving for
to determine their effectiveness and safety in
future clinical applications.
an inclusive ‘HIV cure for all’ that can inactivate
treating CD4+ T cells infected with HIV. They
“We hope to achieve the right balance between
diverse HIV strains across various cellular
shared results from two systems, saCas9 and
efficacy and safety of this cure strategy. Only
contexts,” the Amsterdam team said. With HIV
cjCas. SaCas9 showed outstanding antiviral
then can we consider clinical trials of ‘cure’ in
able to infect different types of cells and tissues in
performance, managing to completely inactivate
humans to disable the HIV reservoir. While these
the body, each with its own unique environment
HIV with a single guide RNA (gRNA) and
preliminary findings are very encouraging, it is
and characteristics, the researchers are searching
excise (cut out) the viral DNA with two gRNAs.
premature to declare that there is a functional
for a way to target HIV in all of these situations.
The strategy of minimising the vector size was
HIV cure on the horizon.”
a new means to target HIV DNA.
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