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While the genetic mutations driving adult cancers can sometimes be targeted with drugs, most pediatric cancers lack good targets. That’s because their driving genetic alterations often create fusion proteins that aren’t easy for drugs to attack.
“This is one reason why it is notoriously hard to make targeted drugs against childhood cancers — their cancer-promoting proteins often lack good pockets for drugs to bind to,” says Kimberly Stegmaier, MD.
However, that’s beginning to change. …
Min Dong, PhD, and his lab are world experts in toxins and how to combat them. They’ve figured out how Clostridium difficile’s most potent toxin gets into cells and zeroed in on the first new botulinum toxin identified since 1969. Now, they’ve set their sights on Shiga and ricin toxins, and not only identified new potential lines of defense, but also shed new light on a fundamental part of cell biology: glycosylation. …
Gene editing has begun to be tested in clinical trials, using CRISPR-Cas9, zinc finger nucleases (ZFN) and other technologies to directly edit DNA inside people’s cells. Multiple trials are in the recruiting or planning stages. But a study in PNAS this week raises a note of caution, finding that person-to-person genetic differences may undercut the efficacy of the gene editing process or, in more rare cases, cause a potentially dangerous “off target” effect.
The study adds to evidence that gene editing may need to be adapted to each patient’s genome, to ensure there aren’t variants in DNA sequence in or near the target gene that would throw off the technology. …
Three-dimensional modeling and CRISPR-Cas9 gene editing technology are giving scientists a new view into Sturge-Weber syndrome, a rare congenital disorder that causes small blood vessels, called capillaries, to be malformed. These capillary malformations can cause port wine birthmarks on the face and neck, and in some cases, abnormal vasculature in the brain that can spark seizures.
Last year, a Boston Children’s Hospital research team — led by Joyce Bischoff, PhD, of the Vascular Biology Program — discovered that the genetic mutation responsible for Sturge-Weber syndrome dwells in endothelial cells lining the affected capillaries in the brain. The team had previously found the same mutation present in the endothelial cells of skin capillaries of patients’ port wine birthmarks.
Together, their studies suggest that mutated endothelial cells could be causing surrounding cells to behave abnormally.
To explore this emerging hypothesis, Bischoff’s team is seeking lifelike ways of mimicking these hallmark capillary malformations in the laboratory. …