In a model of human fetal brain development, Emory researchers can see perturbations of epigenetic markers in cells derived from people with familial early-onset Alzheimer’s disease, which takes decades to appear. This suggests that in people who inherit mutations linked to early-onset Alzheimer’s, it would be possible to detect molecular changes in their brains before birth.
The results were published in the journal Cell Reports.
“The beauty of using organoids is that they allow us to Read more
Why do people with cystic fibrosis (CF) have such trouble with lung infections? The conventional view is that people with CF are at greater risk for lung infections because thick, sticky mucus builds up in their lungs, allowing bacteria to thrive. CF is caused by a mutation that affects the composition of the mucus.
Rabindra Tirouvanziam, an immunologist at Emory, says a better question is: what type of cell is supposed to be fighting the Read more
Many cancer researchers can claim to have devised “smart bombs.” What has been missing is the stealth bomber – a delivery system that can slip through the body’s radar defenses.
Oncolytic viruses, or viruses that preferentially kill cancer cells, have been discussed and tested for decades. An oncolytic virus against melanoma was approved by the FDA in 2015. But against metastatic cancers, they’ve always faced an overwhelming barrier: the human immune system, which quickly captures viruses injected into the blood and sends them to the liver, the body’s garbage disposal.
Researchers at Emory and Case Western Reserve have now circumvented that barrier. They’ve re-engineered human adenovirus, so that the virus is not easily caught by parts of the innate immune system.
A cryo-electron microscopy structure of the virus and its ability to eliminate disseminated tumors in mice were reported on November 25 in Science Translational Medicine.
“The innate immune system is quite efficient at sending viruses to the liver when they are delivered intravenously,” says lead author Dmitry Shayakhmetov, PhD. “For this reason, most oncolytic viruses are delivered directly into the tumor, without affecting metastases. In contrast, we think it will be possible to deliver our modified virus systemically at doses high enough to suppress tumor growth — without triggering life-threatening systemic toxicities.”
A recent paper in Journal of Virology mixes tried-and-true cancer-fighting tactics with the exotic. Sort of a peanut-butter-and-chocolate story, but definitely not tasty!
The tried and true is doxorubicin (Adriamycin), the notorious ‘red devil’ chemotherapy drug, which has been around for decades. On the exotic side, we have oncolytic viruses – viruses retuned to attack cancer cells more than healthy cells. This idea finally made it to FDA approval in 2015 in the form of a re-engineered herpes virus directed against melanoma.
In the JVI paper, graduate students Roxana Rodriguez-Stewart, Jameson Berry and their colleagues infected triple-negative breast cancer cells with a variety of reoviruses, in an effort to select for those that replicate better in those cells. They also looked for drugs that enhance viral infection of those cells, and landed on doxorubicin and related drugs. Doxorubicin is part of a class of anticancer drugs that inhibit topoisomerases, enzymes that unwind DNA as part of the process of replication.
A recent publication from Bill Kaiserâ€™s and Ed Mocarskiâ€™s labs in Cell Host & Microbe touches on a concept that needs explaining: oncolytic viruses.
Viruses have been subverting the machinery of healthy cells for millions of years, and many viruses tend to infect particular tissues or cell types. So they areÂ a natural starting point for researchers to engineer oncolytic viruses, which preferentially infect and kill cancer cells.