The data presented in this study indicate the potential of the CRISPR/Cas9 system as a new therapeutic strategy to combat pathogenic human herpesviruses. The authors Click to expand...

Primitive Antivirals

Molecular Scissorhands

The advances in medical technology are just incredible.Take herpesviruses - the main viruses of interest in chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM). Virtually everyone carries latent herpesviruses in their cells. When these viruses get reactivated they can cause major problems.[fright][/fright]Herpesviruses, for instance, are now being pegged as a likely cause of Alzheimer's. Herpes simplex virus type 1 (HSV-1) causes cold sores, genital herpes and, if Dr. Pridgen is right, fibromyalgia. Varicella-zoster causes shingles, human cytomegalovirus (HCMV) is the most common viral cause of birth defects, and Epstein-Barr virus (EBV) causes infectious mononucleosis, which commonly triggers ME/CFS, and increases one's risk of coming down with multiple sclerosis as well. It is also causes several different types of cancer.The problem with the available anti-herpesvirus drugs is that they target the virus only when it starts replicating. They can't even find the bug when it's in in its latent stage, and have trouble finding it when a low-level infection is present. That means very long antiviral regimens for people with ME/CFS.Plus when some drugs find an herpesvirus infected cell they simply kill the cells. That's fine for many cells but killing a neuron to get rid of a herpesvirus is apparently a bit like burning down a village to save it; it's not something that you want to do if you can avoid itWhat we really need is an approach that can get after herpesviruses in their latent state and destroy them without damaging the cells they've infected. That sounds like wishful thinking but the future isn't what it used to be.In this study a Dutch team from the University Medical Center in Utrecht, The Netherlands,tried to knock out three herpeviruses using genome editing process called CRISPR/Cas9. CRISPR/Cas9 is a part of the adaptive immune response developed by bacteria. It's able to get clipping sequences out of the DNA of pathogens. If it clips enough sequences out the pathogen dies. These Dutch researchers used "guide RNA" to target these molecular scissor on specific gene sequences in herpesviruses in the lab.First they targeted several genes involved in replication of the herpes simplex (HSVI)and cytomegaloviruses. Then they went after several essential genes Epstein-Barr virus (EBV) and HSVI uses to remain in its latent state.[fleft][/fleft]They were able to completely stop all the herpesviruses from replicating and they were able to "clear"; i.e. snuff out up to 95% of the EBV genomes from the target areas. The researchers believe that further optimization of this approach may allow them to completely clear EBV from human cells.The growth of new infectious HSV-1 was so effectively blocked that it resulted in a >106 drop in viral load. Perhaps because of the way HSV -1 is packaged, the researchers were unable to "clear" latent HSV-I infections, however.There was a catch with HCMV as well. After eleven days in culture HCMV started to emerge again as the tricky virus learned to work around the gaps in the viruses DNA the CRISPR/Cas9 approach had produced. The researchers believe they can eliminate this problem targeting more genes.This is clearly a potentially devastating and powerful new weapon in the fight against pathogens. Like any powerful weapon, however, it has the possibility of being a double-edged sword. If the CRISPR/Ca9 system got loose and started "editing" human genes, that would be bad news. It appears that some small of non-pathogen editing does occur but the researchers were unable to find evidence of it. They noted that much work had gone into ensuring that damaging editing does not happen.I don't think that anyone before now has conceived of the possibility of actually completely eliminating these viruses in human.The effects of completely removing a group of viruses that humans have had such an intimate connection with are, of course, unclear.This was basically step one; it took place in the lab - no humans, mice or other laboratory animals involved. The net step will be creating a delivery system that efficiently delivers the editing machinery to infected cells.