A team at Temple University Hospital may soon develop a cure for a disease that affects almost one in six 14 to 49-year-old Americans: herpes.
The team—led by Dr. Pamela Roehm, the principal investigator—is working to reduce the viral infection by using the same technology a separate team of researchers used to successfully disrupt the gene sequences for HIV in 2014.
Graduate and undergraduate students involved in the testing use a “tool” called CRISPR/Cas9 to eliminate one of around 78 essential proteins that make up the herpes virus.
Lifan He, a first-year graduate student in the Health Informatics program, said CRISPR/Cas9 contains the instructions and the tool to cut out a specific protein in the herpes gene sequence, ICP0.
While eliminating ICP0 means the infection and its effects are greatly reduced, there are other parts of the herpes’ DNA without which herpes will not survive. The team has not eradicated any of these genes yet; but they are working on different targets for Cas9. He added the team has successfully eliminated the protein ICP0 from herpes’ gene sequence in the simplest platform of research: human cell lines.
“Once CRISPR/ Cas 9 is in the cell, it works like scissors,” He said. “We cut out ICP0 and once we cut it out, the whole viral infection is reduced.”
Team members, including doctors Masoud Shekarabi, Hassen Wollebo, Anna Bellizzi, Julian Salkind and Kamel Khalili, said as this research progresses, if other proteins respond similarly to ICP0, an eventual cure could be found for herpes.
This team is currently working with herpes simplex Type 1, which is often the strain that causes cold sores around the mouth. The Type 1 strain now commonly manifests as genital herpes as well, Roehm said, because of changing sexual practices, including the increase of oral sex. Both Type 1 and Type 2 have similar gene sequences, and CRISPR could eventually be used to treat Type 2 with some genetic modifications, He said.
“The target I am working on now, which is not ICP0, can potentially beat Type 2 and Type 1 at the same time,” He added.
Roehm said she is interested in finding a cure for herpes simplex Type 1 because it is a common disease.
“When you’re a child, your parents kiss you, your family kisses you and you can be infected,” she said. “The disease often remains dormant for years and this is actually the preferred situation. If you do not acquire the disease as a child and come in contact with it later in life, you don’t have the immunity with which to fight it.”
Roehm is an otolaryngologist and neurologist, working with the head, nose and throat—the areas that can be affected when the dormant herpes virus is reactivated. These areas are also affected with rare diseases like delayed facial palsy and Bell’s palsy when the virus reactivates, she said.
Herpes simplex Type 1 and Type 2 are rare viruses—humans are the only species affected by them.
“With the eradication of herpes simplex in humans, it would mean eradication of the virus completely,” Roehm said.
Roehm added herpes, however, is a “selfish” set of genes, with the sole purpose of replicating and the team of researchers is working to disrupt its gene sequence, which would ultimately lead to a cure, instead of treatment.
Initial research involved testing ICP0 on the cell lines—and because the work has been successful at this level, the team is moving on to deceased rats.
The team is now working with primary neuron cell culture, which means they are now working with neurons in the brain. This level of research is much more complicated than the singular cell line, as they are working with actual subjects instead of home grown cells. Additionally, once the team figures out how to insert Cas9 into the rat’s brain, it still means work to come as a living brain functions differently than a dead one.
“Because it is a tumor cell line, it is not as natural as primary cell culture,” He said. “And primary cell culture is not as natural as a live animal, which is not as close as human.”
Lila Gordon can be reached at lila.gordon@temple.edu.
When we can cure hsv2?