Exosome-based approach reduces levels of HIV in mice
Scientists have used exosomes to deliver a novel protein that prevented HIV from replicating in the bone marrow, spleen and brain of mouse models.
A new study conducted by researchers at the Beckman Research Institute, US, has unveiled a new exosome-based strategy to block HIV replication in mice. The team used exosomes to deliver a novel protein into the cells of mice with HIV and found that the protein attached to HIV’s genetic material and prevented it from replicating, thereby reducing levels of HIV in the bone marrow, spleen and brain.
While much research has aimed to develop new therapies to treat and cure HIV, there are numerous challenges. One challenge 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.
In this study, the researchers use exosomes 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 the team 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,” commented Dr Kevin Morris who led the study.
According to the researchers, these findings demonstrate that exosomes can be used to deliver proteins into HIV-infected cells in the body to silence replication of HIV. In the future, the team 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.
The study was published in Nature Communications.