Short snippets of DNA called aptamers (red) readily get into cancer cells (green and blue) on their own (left panel). They can't penetrate cells when stuck to an oligonucleotide (center), but regain the ability when the oligonucleotide's bonds are broken by UV light (right). (Images courtesy Lele Li, PhD.)
You have a drug. You know what you want it to do and where in the body you need it to go. But when you inject it into a patient, how can you make sure your drug does what you want, where you want, when you want it to?
CRISPR—a gene editing technology that lets researchers make precise mutations, deletions and even replacements in genomic DNA—is all the rage among genomic researchers right now. First discovered as a kind of genomic immune memory in bacteria, labs around the world are trying to leverage the technology for diseases ranging from malaria to sickle cell disease to Duchenne muscular dystrophy.
In a paper published yesterday in Cell Stem Cell, a team led by Derrick Rossi, PhD, of Boston Children’s Hospital, and Chad Cowan, PhD, of Massachusetts General Hospital, report a first for CRISPR: efficiently and precisely editing clinically relevant genes out of cells collected directly from people. Specifically, they applied CRISPR to human hematopoietic stem and progenitor cells (HSPCs) and T-cells.
“CRISPR has been used a lot for almost two years, and report after report note high efficacy in various cell lines. Nobody had yet reported on the efficacy or utility of CRISPR in primary blood stem cells,” says Rossi, whose lab is in the hospital’s Program in Cellular and Molecular Medicine. “But most researchers would agree that blood will be the first tissue targeted for gene editing-based therapies. You can take blood or stem cells out of a patient, edit them and transplant them back.”
The study also gave the team an opportunity to see just how accurate CRISPR’s cuts are. Their conclusion: It may be closer to being clinic-ready than we thought. Full story »
Dolly the sheep, the first mammalian example of successful somatic cell nuclear transfer. (Toni Barros/Wikimedia Commons)
We all remember Dolly the sheep, the first mammal to be born through a cloning technique called somatic cell nuclear transfer (SCNT). As with the thousands of other SCNT-cloned animals ranging from mice to mules, researchers created Dolly by using the nucleus from a grown animal’s cell to replace the nucleus of an egg cell from the same species.
The idea behind SCNT is that the egg’s cellular environment kicks the transferred nucleus’s genome into an embryonic state, giving rise to an animal genetically identical to the nucleus donor. SCNT is also a technique for generating embryonic stem cells for research purposes.
While researchers have accomplished SCNT in many animal species, it could work better than it does now. It took the scientists who cloned Dolly 277 tries before they got it right. To this day, SCNT efficiency—that is, the percent of nuclear transfers it takes generate a living animal—still hovers around 1 to 2 percent for mice, 5 to 20 percent in cows and 1 to 5 percent in other species. By comparison, the success rate in mice of in vitro fertilization (IVF) is around 50 percent.
Blood-forming hematopoietic stem cells (top) give rise to all blood and immune cell types. In children with SCID, the steps leading to immune cells are broken.
In the world of fatal congenital immunodeficiency diseases, good news is always welcome, because most patients die before their first birthday if not treated. Babies with severe combined immunodeficiency disease, aka SCID or the “bubble boy disease,” now have more hope for survival thanks to two pieces of good news.
The Ebola situation in Dallas—with one patient death, two nurse exposures, dozens under quarantine, and talk last week of declaring a state of emergency in the city—has thrown into stark relief the gaps between public health and frontline clinical care. But those gaps also present opportunities to make public health data work harder and to change how doctors approach clinical care in times when events and information are changing at Internet speed.
It comes down to making electronic health records (EHRs) work more flexibly, in ways that help promote situational awareness among clinicians during times of crisis and flag instances when a patient’s condition may require more attention than usual. Full story »
What all of these things have in common is data. Lots of it. Some of it represents kinds of data that didn’t exist 5 or 10 years ago, but all of it is slowly beginning to fuel the pharma sector’s efforts to create the next blockbuster drug or targeted therapeutic.
This winter, if your doctor suggests that you take Tamiflu, you might want to ask for a conflict of interest statement: a new study suggests that doctors who received payments from the makers of flu-fighting neuraminidase inhibitors—drugs like Tamiflu® and Relenza®—were more likely to view the drugs’ prowess in a favorable light.
You are what you eat, the saying goes. For some conditions (think cardiovascular disease or type 2 diabetes), there are clear connections between diet, health and illness.
For breast cancer, the picture is less clear. Many epidemiologic and laboratory studies have examined the Western diet (in particular, cholesterol) and its relation to breast cancer, with conflicting results.
“There’s been a raging debate in the field,” says Christine Coticchia, PhD, who works in the laboratory of Boston Children’s Hospital’s Vascular Biology Program director, Marsha Moses, PhD. “The biology of cancer and of cholesterol are so complex, and there are many subsets of breast cancer. In order to find any connections, you have to ask very specific questions.”
Banding together with Keith Solomon, PhD, in Boston Children’s Urology Department, Coticchia and Moses asked whether dietary cholesterol might encourage progression of the most aggressive, so-called “triple-negative” breast tumors. As they report in the American Journal of Pathology, they found a big impact, at least in mice. But it’s too early to say just yet that cutting back on cholesterol will help women avoid breast cancer. Full story »