Progress is being made in laboratory studies

MIT News

Published May 13 in Nature Communications, Jerome and his Fred Hutch team published an encouraging step toward a gene therapy for herpes.
The experimental gene therapy involves injecting into the blood a mixture of gene editing molecules that seek out where the herpes virus resides in the body.
Once the vector reaches the clusters of nerves where the herpes virus hangs out, the molecular scissors snip away at the herpes virus’s genes to damage them or remove the virus entirely.
In addition, the researchers found that the HSV-1 gene therapy had a significant reduction in both the frequency and amount of viral shedding.
The Fred Hutch team also simplified their gene editing treatment, making it safer and easier to make.
“Our streamlined gene editing approach is effective at eliminating the herpes virus and has less side effects to the liver and nerves,” Jerome said.
They also noted that though the current study examined HSV-1 infections, they are working on adapting the gene editing technology to target HSV-2 infections.
“We’re collaborating with numerous partners as we approach clinical trials so we align with federal regulators to ensure safety and effectiveness of the gene therapy,” Jerome said.

POSITIVE

Pre-clinical studies conducted by researchers at Fred Hutch Cancer Center revealed that an experimental gene therapy for genital and oral herpes eliminated 90 percent or more of the infection and suppressed the amount of virus that could be released from an infected person, suggesting that the therapy would also lessen the virus’s ability to spread.

“Herpes can be very cunning. It burrows itself into nerve cells, reawakens, and produces excruciating skin blisters,” stated Keith Jerome, MD, Ph.D. C. professor at Fred Hutch in the division of infectious diseases and vaccines. “We want to rid people of this infection so they won’t have to worry about outbreaks or spreading it to other people.”. “.

A promising step toward herpes gene therapy was published by Jerome and his colleagues at Fred Hutch on May 13 in Nature Communications.

A combination of gene editing molecules that seek out the location of the herpes virus in the body are injected into the blood as part of an experimental gene therapy treatment. The combination contains enzymes that function similarly to molecular scissors along with laboratory-modified viruses known as vectors, which are frequently utilized in gene therapies. The molecular scissors cut away at the herpes virus’s genes to either harm or eradicate the virus completely once the vector reaches the nerve clusters where the herpes virus congregates.

Martine Aubert, Ph., the first author, stated, “We are using a meganuclease enzyme that cuts in two different places in the DNA of the herpes virus.”. D. lead staff scientist at Fred Hutch. The virus can’t heal itself because of the extensive damage caused by these cuts. Next, the damaged DNA is identified as alien by the body’s own repair mechanisms, which eliminate it. ****.

Ninety-nine percent of herpes simplex virus 1 (HSV-1) after facial infection, also known as oral herpes, and ninety-seven percent of HSV-1 after genital infection were killed by the experimental therapy using mouse models of the infection. The treated mice did not exhibit these reductions for about a month, and the reduction of virus appeared to be more thorough over time.

Furthermore, the researchers discovered that the frequency and volume of viral shedding were significantly decreased by the HSV-1 gene therapy.

Speaking with those who have herpes, Jerome noted that many are concerned about the virus spreading to others. According to our most recent research, we can lower the quantity of virus that resides in the body as well as the amount that is shed. “.”.

The Fred Hutch group also made their gene editing procedure simpler, safer, and more straightforward. Three vectors and two distinct meganucleases were employed in a 2020 study. The most recent work employs a single vector and a single meganuclease that can split the virus’s DNA in two different locations.

“With less adverse effects on the liver and nerves, our streamlined gene editing approach effectively eradicates the herpes virus,” Jerome stated. This implies that because the therapy has fewer ingredients, it will be simpler to prepare and safer for patients. ****.

The Fred Hutch scientists are excited to apply their research to human treatments and are inspired by the success of gene therapy in animal models; however, they are cautious about the procedures that must be followed in order to get ready for clinical trials. They added that while HSV-1 infections were the focus of the current study, efforts are underway to modify the gene editing technology to target HSV-2 infections.

To guarantee the efficacy and safety of the gene therapy, Jerome stated, “We’re aligning with federal regulators as we approach clinical trials by working with numerous partners.”. As they share our goal of eradicating this infection, we are incredibly grateful for the support of herpes advocates. “.

After an individual contracts the herpes simplex virus (HSV), the infection is contagious and can last a lifetime. Current treatments only manage symptoms, such as excruciating blisters, rather than curing them entirely. The World Health Organization estimates that 31.7 billion people under 50 (or 67% of the population) are infected with HSV-1, the virus that causes oral herpes. HSV-2, the virus that causes genital herpes, is thought to affect 491 million people worldwide, or 13% of those between the ages of 15 and 49.

Further health risks can be caused by herpes. The chance of contracting HIV is raised by HSV-2. HSV-1 and dementia have been related in other studies.

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