How gene editing eliminates HIV-1 infection, cancer, by studies
*Filthy habit could prevent cavities, stomach ulcers, AIDS
A permanent cure for Human Immuno-deficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) infection remains elusive due to the virus’s ability to hide away in latent reservoirs. But now, in new research published in print May 3 in the journal Molecular Therapy, scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) and the University of Pittsburgh show that they can excise HIV Deoxy Nucleic Acid (DNA)/genetic material from the genomes of living animals to eliminate further infection. They are the first to perform the feat in three different animal models, including a “humanized” model in which mice were transplanted with human immune cells and infected with the virus.
The team is the first to demonstrate that HIV-1 replication can be completely shut down and the virus eliminated from infected cells in animals with a powerful gene editing technology known as CRISPR/Cas9. The work was led by Wenhui Hu, MD, PhD, currently Associate Professor in the Center for Metabolic Disease Research and the Department of Pathology (previously in the Department of Neuroscience) at LKSOM; Kamel Khalili, PhD, Laura H. Carnell Professor and Chair of the Department of Neuroscience, Director of the Center for Neurovirology, and Director of the Comprehensive NeuroAIDS Center at LKSOM; and Won-Bin Young, PhD. Dr. Young was Assistant Professor in the Department of Radiology at the University of Pittsburgh School of Medicine at the time of the research. Dr. Young recently joined LKSOM.
The new work builds on a previous proof-of-concept study that the team published in 2016, in which they used transgenic rat and mouse models with HIV-1 DNA incorporated into the genome of every tissue of the animals’ bodies. They demonstrated that their strategy could delete the targeted fragments of HIV-1 from the genome in most tissues in the experimental animals.
“Our new study is more comprehensive,” Hu said. “We confirmed the data from our previous work and have improved the efficiency of our gene editing strategy. We also show that the strategy is effective in two additional mouse models, one representing acute infection in mouse cells and the other representing chronic, or latent, infection in human cells.”
Also, a novel gene therapy using CRISPR genome editing technology effectively targets cancer-causing “fusion genes” and improves survival in mouse models of aggressive liver and prostate cancers, University of Pittsburgh School of Medicine researchers report in a study published online in Nature Biotechnology.
“This is the first time that gene editing has been used to specifically target cancer fusion genes. It is really exciting because it lays the groundwork for what could become a totally new approach to treating cancer,” explained lead study author Jian-Hua Luo, M.D., Ph.D., professor of pathology at Pitt’s School of Medicine and director of its High Throughput Genome Center.
Fusion genes, which often are associated with cancer, form when two previously separate genes become joined together and produce an abnormal protein that can cause or promote cancer.
Luo and his team had previously identified a panel of fusion genes responsible for recurrent and aggressive prostate cancer. In a study published earlier this year in the journal Gastroenterology, the team reported that one of these fusion genes, known as MAN2A1-FER, also is found in several other types of cancer, including that of the liver, lungs and ovaries, and is responsible for rapid tumor growth and invasiveness.
In the current study, the researchers employed the CRISPR-Cas9 genome editing technology to target unique DNA sequences formed because of the gene fusion. The team used viruses to deliver the gene editing tools that cut out the mutated DNA of the fusion gene and replaced it with a gene that leads to death of the cancer cells. Because the fusion gene is present only in cancer cells, not healthy ones, the gene therapy is highly specific. Such an approach could come with significantly fewer side effects when translated to the clinic, which is a major concern with other cancer treatments such as chemotherapy.
Meanwhile, a study has revealed people who pick their noses may actually be healthier – giving good reason for children to carry on with the disgusting habit.
Austrian lung specialist Professor Friedrich Bischinger, said: “Eating the dry remains of what you pull out is a great way of strengthening the body’s immune system. Medically it makes great sense and is a perfectly natural thing to do.
“In terms of the immune system, the nose is a filter in which a great deal of bacteria are collected, and when this mixture arrives in the intestines it works just like a medicine.”
Scientists from Harvard University and the Massachusetts Institute of Technology found that nasal mucus’ rich reservoir of ‘good’ bacteria prevents cavity-causing bacteria from sticking to teeth.
Published in the American Society for Microbiology, their findings also suggest snot could defend against respiratory infections, stomach ulcers and even HIV.
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