Scientists intend to attack the herpes virus DNA using the CRISPR / Cas9 genome editing technology. This will help suppress the replication of the pathogen and remove it.
NETHERLANDS – The CRISPR / Cas9 technique allows rewrite of the genetic message by cutting specific DNA sequences, in virtually any region. Recently, these powerful molecular scissors have obtained approval from the National Institutes of Health US to design immune cells that can fight cancer in humans. Its potential yet to be explored which can revolutionize biomedicine.
The team of Robert Jan Lebbink from University Medical Center Utrecht thought of using the CRISPR / Cas9 system to mutate the DNA of latent herpes virus in infected human cells and thus prevent associated diseases.
The researchers devised RNA sequences that serve as a guide, complementary to the vital parts of the virus genome and operated as ‘molecular guidelines’.
These RNA-guide, combined with the molecular scissors CRISPR / Cas9 system, create specific cuts in the herpesvirus DNA, that once mutated, it is paralyzed. The authors of the study, published today in PLOS Pathogens, hope that the findings allow designing effective therapeutic strategies to combat human herpesvirus both during the latent period and infection.
The researchers studied three different members of the herpesvirus family: herpes simplex virus type 1 (HSV-1) which causes cold sores and keratitis; human cytomegalovirus (CMV), the most common viral cause of birth defects, when the virus is transmitted from mother to fetus-; and Epstein-Barr virus (EBV), which causes infectious mononucleosis and multiple cancers.
First, the experts worked with cells latently infected lymphoma EBV and showed that the introduction of these RNA-guide specifically targeting DNA sequences with the virus are capable of introducing mutations into selected places.
Such mutations would eliminate essential functions of the virus and viral destabilizatio DNA molecules. Thus, by using two guide RNA could induce the loss of more than 95% of the infected host cell genomes.
Furthermore, the authors observed that, with the appropriate RNA-guide, the CRISPR / Cas9 issue may affect HCMV replication. However, the appearance of variants that edition was omitted, suggested that the simultaneous cutting and pasting of multiple critical sites of HCMV genome is necessary to prevent the development of resistant genomes.
In addition, the experts found that, compared with HCMV, HSV-1 is multiplied much faster. However, when the researchers tested several RNA-directed guide to different essential genes of HSV-1 in conjunction with CRISPR / Cas9, many of them were able to reduce virus replication.
Most adults carries several types of herpes viruses. After the initial acute infection, these viruses establish lifelong infections in their hosts and cause cold sores, keratitis, genital herpes, infectious mononucleosis and other diseases. Even some of these viruses can cause cancer in humans.
During the latent phase of infection, viruses lie dormant for long periods of time, but retain the ability to cause occasional reactivations, which can also lead to disease.