Researchers use exosome-based strategy to block HIV in mice
Study finds reduced levels of HIV in bone marrow, spleen, and brain after therapy

Date:
September 21, 2021
Source:
NIH/National Institute of Mental Health
Summary:
Researchers used exosomes, tiny nanoparticles capable of being
taken up by cells, to deliver novel protein into the cells of mice
infected with HIV. The protein attached to HIVs' genetic material
and prevented it from replicating, resulting in reduced levels of
HIV in the bone marrow, spleen, and brain. The study paves the way
for the development of novel delivery systems for suppressing HIV.



FULL STORY ==========================================================================
In a new study supported by the National Institutes of Health, researchers
used exosomes, tiny nanoparticles capable of being taken up by cells,
to deliver novel protein into the cells of mice infected with HIV. The
protein attached to HIVs' genetic material and prevented it from
replicating, resulting in reduced levels of HIV in the bone marrow,
spleen, and brain. The study, funded by NIH's National Institute of
Mental Health (NIMH) and published in Nature Communications, paves the
way for the development of novel delivery systems for suppressing HIV.


========================================================================== "These results demonstrate the potential of exosome engineering for
delivering epigenetics-based therapeutics capable of silencing HIV gene expression into brain tissues -- an area where HIV has traditionally
been able to hide from HIV treatments," said Jeymohan Joseph, Ph.D.,
chief of the HIV Neuropathogenesis, Genetics, and Therapeutics Branch
within NIMH's Division of AIDS Research.

HIV attacks the immune system by infecting a type of white blood cell
in the body that is vital to fighting off infection. Without treatment,
HIV can destroy these white blood cells, reducing the body's ability
to mount an immune response -- eventually resulting in AIDS. Although researchers have been working to develop new therapies to treat and cure
HIV and AIDS, this quest is challenging for many reasons. One reason is
that HIV can enter a dormant-like state, hiding in the body and evading treatments, only to reactivate at a later date. HIV hiding in the brain
is particularly difficult to access, as the blood-brain barrier often
prevents treatments from entering into those tissues.

One avenue researchers have been pursuing in their efforts to try to cure
HIV is what is sometimes called a "block and lock" approach, particularly
for targeting HIV in the brain. This method attempts to block the virus' ability to replicate itself and lock it in its dormant state.

Kevin Morris, Ph.D., of City of Hope and the Menzies Health Institute Queensland at Griffith University, Australia, led an investigation into
a new approach for blocking and locking HIV in mice. The researchers
use exosomes, tiny nanoparticles capable of being taken up by cells,
to deliver a novel recombinant anti-HIV protein, called ZPAMt, into
cells infected with HIV. The ZPAMt protein was designed by researchers
to attach to a region of the virus called LTR that is critical for virus replication. The protein has an epigenetic marker in it that changes the
way HIVs' genetic information is expressed, suppressing it, and making
the virus unable to divide and multiply.

The exosomes are able to cross the blood brain barrier and enter into the
brain making this treatment capable of targeting this hard-to-reach organ.

When researchers administered this exosome-based treatment to mice
infected with HIV, they found that the exosome-delivered protein was
capable of silencing the HIV-infected cells and that the HIV-infected
mice showed suppression of HIV expression in the bone marrow, spleen,
and brain.

"This exciting body of work demonstrates we can deliver therapeutic
payloads to HIV-infected cells systemically using exosomes. This is an innovative technology that could be a future delivery method for use not
only in HIV but also for treating various other diseases of the brain
such as Parkinson's, Alzheimer's, and addiction," said Dr. Morris.

These findings demonstrate that exosomes can be used to deliver proteins
into HIV-infected cells in the body -- including the hard-to-reach
brain -- to silence replication of HIV. In the future, the researchers
hope to continue their work by using exosomes to deliver gene-excision machinery capable of cutting the HIV out of the genome of infected
people. In addition, they plan to study the use of exosomes to deliver treatments that can assist anti-HIV CAR T- cells in killing HIV-infected
cells. Ultimately, the researchers hope to expand the use of exosomes
beyond HIV -- for instance, to target and control factors associated
with drug addiction.

========================================================================== Story Source: Materials provided by
NIH/National_Institute_of_Mental_Health. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Surya Shrivastava, Roslyn M. Ray, Leo Holguin, Lilliana Echavarria,
Nicole Grepo, Tristan A. Scott, John Burnett, Kevin
V. Morris. Exosome- mediated stable epigenetic repression
of HIV-1. Nature Communications, 2021; 12 (1) DOI:
10.1038/s41467-021-25839-2 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210921172658.htm

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