Scientific Discovery: Researchers Delete HIV From Human Cells
Scientific Discovery: Researchers Delete HIV From Human Cells
Scientists have recently discovered how to delete HIV from human cells . This is the first concrete breakthrough in the massive fight against AIDS. Once the human cell has been conquered by the HIV, it remains there forever. The virus inserts a deadly genome into the DNA of the victims and forces them to be on drugs for the rest of their lives. Now for the first time, scientists have found the means to eliminate the latent HIV-1 virus from human cells and this could also cure latent infections.
The research team at the Temple University School of Medicine have found a way to delete the integrated HIV-1 genes in a permanent way. "This is one important step on the path toward a permanent cure for AIDS," according Kamel Khalili, professor and chair of the department of Neuroscience at Temple as per media reports. Khalili has led the team which has succeeded in its first successful attempt to eliminate latent HIV-1 virus from human cells."It's an exciting discovery, but it's not yet ready to go into the clinic. It's a proof of concept that we're moving in the right direction," Khalili was quoted by media reports as saying.
When it has been deployed, the combination of a DNA-sniping enzyme called a nuclease and the targeting strand of RNA called guide RNA/gRNA has aimed to hunt down the viral genome and excise the HIV-1 DNA. It is from this point that the gene repair machinery of the cell takes over and solders the loose ends of the genome to result in virus-free cells.
According to Khalili, "Since HIV-1 is never cleared by the immune system, removal of the virus is required in order to cure the disease”. The research focuses on the neuropathogenesis of viral infections. The same technique could in theory be used against a variety of viruses according to the research expert.
The research demonstrates that these molecular tools also hold value as a therapeutic vaccine; Cells armed with the nuclease-RNA combination proved resistant to HIV infection. Currently more than 33 million people in the world are suffering from HIV-AIDS . While highly active anti-retroviral therapy/HAART has controlled HIV-1 for infected persons in the developed world over the past 15 years , the virus can continue to persist without any cessation.
While HIV-1 replication is under control through HAART, there is a lingering HIV-1 presence which has terrible consequences for human health.
"The low level replication of HIV-1 makes patients more likely to suffer from diseases usually associated with aging," Khalili indicated. The diseases include cardiomyopathy that is the a weakening of the heart muscle as well as bone disease, kidney disease, and neuro-cognitive disorders. "These problems are often exacerbated by the toxic drugs that must be taken to control the virus," according to Khalili.
Researchers based the two-part HIV-1 editor on a system that came about as a bacterial defense mechanism to protect against infection, Khalili indicated.
Dr Khalili's lab engineered a 20-nucleotide strand of gRNA . This then targets the HIV-1 DNA and pairs it with Cas9. The gRNA targets the control region of the gene referred to as the long terminal repeat/LTR. LTRs are present on both sides of the HIV-1 genome. By targeting both LTRs, the Cas9 nuclease cann erase the 9,709-nucleotides that comprise the HIV-1 genome.
To prevent the risk of the gRNA accidentally binding with any part of the patient's genome, the researchers selected nucleotide sequences that were not present in any coding sequences of human DNA, thereby leading to avoidance of off-target effects and subsequent cellular DNA damage.
The editing process proved successful in various cell types that can harbor HIV-1, including microglia and macrophages, and in T-lymphocytes.
"T-cells and monocytic cells are the main cell types infected by HIV-1, so they are the most important targets for this technology," Khalili explained. The HIV-1 eradication approach faces several significant challenges and only when these are overcome will the technique be ready for patients, Khalili said.
The researchers now aim to devise a method to deliver the therapeutic agent to each single infected cell. Finally, as HIV-1 is prone to mutations, treatment may be required for individualisation for each patient's unique viral sequences.
"We are working on a number of strategies so we can take the construct into preclinical studies," Khalili remarks "We want to eradicate every single copy of HIV-1 from the patient. That will cure AIDS. I think this technology is the way we can do it".
