New gene therapy approach eliminates at least 90% latent herpes simplex
virus

Date:
August 18, 2020
Source:
Fred Hutchinson Cancer Research Center
Summary:
Infectious disease researchers have used a gene editing approach
to remove latent herpes simplex virus 1, or HSV-1, also known as
oral herpes. In animal models, the findings show at least a 90
percent decrease in the latent virus, enough researchers expect
that it will keep the infection from coming back.



FULL STORY ========================================================================== Infectious disease researchers at Fred Hutchinson Cancer Research Center
have used a gene editing approach to remove latent herpes simplex virus 1,
or HSV-1, also known as oral herpes. In animal models, the findings show
at least a 90 percent decrease in the latent virus, enough researchers
expect that it will keep the infection from coming back.


==========================================================================
The study, published August 18 in Nature Communications, used two sets
of genetic scissors to damage the virus's DNA, fine-tuned the delivery
vehicle to the infected cells, and targeted the nerve pathways that
connect the neck with the face and reach the tissue where the virus lies dormant in individuals with the infection.

"This is the first time that scientists have been able to go in and
actually eliminate most of the herpes in a body," said senior author
Dr. Keith Jerome, professor in the Vaccine and Infectious Disease Division
at Fred Hutch. "We are targeting the root cause of the infection: the
infected cells where the virus lies dormant and are the seeds that give
rise to repeat infections." Most research on herpes has focused on
suppressing the recurrence of painful symptoms, and Jerome said that
his team is taking a completely different approach by focusing on how
to cure the disease.

"The big jump here is from doing this in test tubes to doing this in
an animal," said Jerome, who also leads the Virology Division at UW
Medicine. "I hope this study changes the dialog around herpes research
and opens up the idea that we can start thinking about cure, rather than
just control of the virus." Two-thirds of the world population under
the age of 50 have HSV-1, according to the World Health Organization. The infection primarily causes cold sores and is lifelong.



==========================================================================
In the study, the researchers used two types of genetic scissors to cut
the DNA of the herpes virus. They found that when using just one pair
of the scissors the virus DNA can be repaired in the infected cell. But
by combining two scissors -- two sets of gene-cutting proteins called meganucleases that zero in on and cut a segment of herpes DNA -- the
virus fell apart.

"We use a dual meganuclease that targets two sites on the virus DNA,"
said first author Martine Aubert, a senior staff scientist at Fred
Hutch. "When there are two cuts, the cells seem to say that the virus
DNA is too damaged to be repaired and other molecular players come in to
remove it from the cell body." The dual genetic scissors are introduced
into the target cells by delivering the gene coding for the gene-cutting proteins with a vector, which is a harmless deactivated virus that can
slip into infected cells. The researchers injected the delivery vector
into a mouse model of HSV-1 infection, and it finds its way to the target
cells after entering the nerve pathways.

The researchers found a 92% reduction in the virus DNA present in
the superior cervical ganglia, the nerve tissue where the virus lies
dormant. The reductions remained for at least a month after the treatment
and is enough the researchers say to keep the virus from reactivating.

The team did other comparisons to fine-tune the gene editing approach:
* - Gene cuts with meganucleases were more efficient that with
CRISPR/Cas9.

- Refining the vector delivery mechanism, they found the
adeno-associated virus (AAV) vector that was the most efficient
at getting the gene edits to cells infected with the virus.

The researchers are pursuing a similar strategy for herpes simplex 2,
which causes genital herpes. They expect it to take at least 3 years to
move toward clinical trials.

"This is a curative approach for both oral and genital HSV infection,"
Aubert said. "I see it going into clinical trials in the near future."

========================================================================== Story Source: Materials provided by
Fred_Hutchinson_Cancer_Research_Center. Original written by Sabin
Russell. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Martine Aubert, Daniel E. Strongin, Pavitra Roychoudhury,
Michelle A.

Loprieno, Anoria K. Haick, Lindsay M. Klouser, Laurence Stensland,
Meei- Li Huang, Negar Makhsous, Alexander Tait, Harshana S. De Silva
Feelixge, Roman Galetto, Philippe Duchateau, Alexander L. Greninger,
Daniel Stone, Keith R. Jerome. Gene editing and elimination of
latent herpes simplex virus in vivo. Nature Communications, 2020;
11 (1) DOI: 10.1038/s41467- 020-17936-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200818094019.htm

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