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Researchers at the Broad and the Flatiron Institute show how two key cell types in the brain’s cortex arise from a single progenitor, providing clues into how cellular diversity emerges in the brain. Because many neurodevelopmental and psychiatric disorders affect different cell types differently, the authors say their work could also help researchers better understand how these disorders come about.
Some gene therapies that use harmless, gene-shuttling viruses have shown promise in treating some forms of some muscular dystrophies, but they’ve faced significant challenges. High doses of the gene-carrying virus are needed to reach the muscles throughout the body and the viruses used in clinical trials often end up in the liver more than in the muscle. This has led to high levels of the virus in the liver, severe adverse side effects, and even death in some clinical trial participants. A team of researchers from the Broad, Harvard University, and Boston Children's Hospital has developed a family of viral vectors called MyoAAV. MyoAAV is 10 times more efficient at delivering genetic cargo to mouse, primate, and human muscle cells than those currently used in clinical trials and avoids the liver. The team showed that, because of this increased efficiency, MyoAAV can be used to deliver therapeutic genes at around 100 to 250 times lower doses than other viral vectors used in other studies and trials, potentially reducing the risk of liver damage and other serious side effects.
A tumor in the human body is like a city at war, bustling with cancer cells, immune cells, blood vessels, signaling molecules and surrounding tissue. A simple census of these players will provide some basic information on their battle, but won’t tell you their organization or strategy. A team of researchers from the Broad, Massachusetts General Hospital, the Evergrande Center for Immunologic Diseases at Brigham and Women's Hospital and Harvard Medical School, and Dana-Farber Cancer Institute has gained new insight into this organization. They have discovered that immune cells in some human colorectal tumors gather together in clusters, like soldiers mobilizing in formation. By using a unique combination of single-cell and imaging technologies, along with newly developed data analytical approaches, the scientists found a level of spatial organization of cells not observed before in tumors.
Researchers from Massachusetts Institute of Technology (MIT), the McGovern Institute for Brain Research at MIT, the Howard Hughes Medical Institute, and the Broad Institute of MIT and Harvard have developed a new way to deliver molecular therapies to cells. The system, called SEND, can be programmed to encapsulate and deliver different RNA cargoes. SEND harnesses natural proteins in the body that form virus-like particles and bind RNA, and it may provoke less of an immune response than other delivery approaches.
“I want to tell students who are interested in interdisciplinary research to not be afraid of feeling like you don’t belong to a specific community. Instead, think of the intersection of fields as your intellectual home,” says Hoon Cho, a computational biologist who researches techniques to strengthen biomedical privacy. In a #WhyIScience Q&A, Cho talks about his work using computational techniques to give individuals more control over their biomedical privacy and his work at the intersection of computer science and biomedicine.
A rare population of cancer cells called cycling persister cells resist drug treatment and even maintain the ability to grow and proliferate. Scientists think these cells may contribute to cancer recurrence. Now, a team of researchers at Harvard Medical School and the Broad have developed a labeling system called Watermelon to to track such cells, learn more about their metabolic and RNA profiles, identify new pathways for intervention, and potentially shed light on why some therapeutics that seem promising in the lab fail in the clinic. The results, published in Nature, could help researchers design therapies to delay or ultimately prevent recurrence by targeting cycling persister cells specifically.
Risk of infection increases dramatically as a person ages, but scientists do not yet fully understand the link between advanced age and immunity. A team of researchers led by Broad associate member Pradeep Natarajan, in collaboration with Massachusetts General Hospital, Harvard Medical School, Yale University, and National Cancer Institute, examined genetic and clinical data from nearly 800,000 patients, finding that those with mosaic chromosomal alterations, an acquired rearrangement in white blood cell chromosomes, were more likely to develop severe infections such as sepsis, severe COVID-19, and other pneumonias. “It’s important for us to continue to understand who is at risk for severe infections,” said Natarajan. “The way that we assess that risk today is largely just by age. This work helps us refine that much more and may help in future public health efforts.”
Sickle cell disease is the most common deadly genetic disorder, affecting more than 300,000 newborns worldwide each year and leading to chronic pain, organ failure, and early death. Combining expertise in protein engineering, base editing, and red blood cell biology, a team at Broad and St. Jude Children's Research Hospital has developed a gene editing approach to correct the mutation underlying sickle cell disease in mice. The team hopes that this work will provide a promising basis for a therapeutic strategy down the road for sickle cell disease.
As a senior at Harvard and researcher at Broad, Esther Elonga has already had her fair share of adventure. Her family fled the war-torn Democratic Republic of Congo when she was three years old and lived as refugees in Uganda for 13 years before moving to the United States and settling in Concord, New Hampshire. Two years later, Elonga earned a full scholarship to Harvard University, where she majored in chemistry while conducting translational research at Broad. She is now about to embark on the next stage of her adventure, beginning an MD-PhD program at Stanford University this fall. Elonga recently spoke with us about her educational path, what is inspiring her to become a physician-scientist, and the people who supported her throughout her journey in a #WhyIScience Q&A.
Researchers have found a range of molecular and genomic changes in individual SARS-CoV-2-infected cells from 17 patients who died of COVID-19. The team also saw signs of multiple, unsuccessful attempts of the lungs to repair themselves in response to respiratory failure. The team used single-cell RNA sequencing data from tissue samples taken from 11 organ systems—including the lungs, heart, liver, and kidneys—to build a comprehensive atlas of hundreds of thousands of individual cells showing how COVID-19 can lead to organ failure and death. This was a collaboration with (tag) Mass General, Ragon Institute, MIT, Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Columbia University Irving Medical Center.
