Progress towards a definitive therapy against herpes simplex, the virus that causes annoying and recurrent blisters on the lips, belonging to the same ‘family’ responsible for the genital infection. Scientists from the Fred Hutch Cancer Center in Seattle (USA) have in fact demonstrated, in preclinical studies, that an experimental gene therapy for cold sores was able to remove more than 90% of the virus from the body, according to data published in ‘Nature Communications’ by the team led by Keith Jerome, researcher in the Vaccines and Infectious Diseases division at ‘Fred Hutch’.
“Herpes – explained Jerome – is very sneaky. It hides between nerve cells and then wakes up and causes painful blisters on the skin that many experience. Our goal is to finally cure people of this infection”. There experimental gene therapy involves the injection into the blood of a mixture of genetic editing molecules – technology that allows the individual ‘letters’ of DNA to be corrected in a targeted and precise way – which ‘search’ for the herpes virus in the body. The injected mix contains laboratory-modified viruses that act as vectors, as well as enzymes that work like molecular scissors. Once the vector reaches the sites where the herpes virus is located, molecular scissors cut away the virus’s genes to damage them so as to make them ineffective or remove them permanently.
“We are using – highlighted the first author of the study, Martine Aubert – a meganuclease enzyme that cuts the DNA of the herpes virus at two different points. These cuts damage the virus so much that it cannot repair itself. Therefore the repair systems of the body recognize the damaged DNA as foreign and get rid of it.” Using mouse models of the infection, experimental therapy it eliminated 90% of the virus of herpes simplex 1 (Hsv-1, which mainly affects the lips) after labial infection, and 97% of Hsv-1 after genital infection. It took about a month for the treated mice to show these reductions, and the virus reduction appeared to become more complete over time. Additionally, the researchers found that gene therapy for HSV-1 had a significant reduction in both the frequency and amount of viral shedding.
“If you talk to people who live with herpes – underlined Jerome – many are worried about the fact that their infection could be transmitted to others. Our new study – added the scientist who has been working on this line of research for years research – shows that we can reduce both the amount of virus inside the body and the amount of virus that is eliminated.” The Fred Hutch team also simplified the gene editing treatment, making it safer and easier to perform. In a 2020 study the research team used three vectors and two different meganucleases. The latest study uses a single vector and a meganuclease capable of cutting the virus’s DNA in two places.
“Our simplified approach to gene editing – Jerome specified – it is effective in eliminating the herpes virus and has fewer side effects on the liver and nerves. The therapy, therefore, will be safer for people and easier to carry out, since it contains fewer ‘ingredients'”. Fred Hutch scientists consider the results obtained encouraging, but to translate the results into treatments for people it is necessary to focus now on clinical studies. At the same time, researchers are working to adapt gene editing technology to also target Hsv-2 infections, and not just Hsv-1 as done so far.
The herpes simplex virus is a common, lifelong infection once people become infected. Current therapies can only suppress, but not completely eliminate symptoms, including painful blisters. According to the World Health Organization, approximately 3.7 billion people under the age of 50 (67%) have HSV-1, which causes oral herpes. An estimated 491 million people aged 15 to 49 (13%) worldwide have HSV-2, which causes genital herpes.
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