The week’s most astounding developments from the neobiological frontier.

September 9, 2021

Better targeting in gene therapy

One of the most critical challenges in gene therapy is the specificity of delivery: How to target therapeutic replacement genes to their intended tissues—but only those tissues. It’s like giving a pizza man an exact street address as opposed to having them drop off pies at any white-picket-fence house along the way. Now a team of researchers at Harvard University has developed a way to use directed evolution to engineer small adeno-associated virus vectors, a standard FDA-approved platform for gene therapy, to target skeletal muscle cells in mice and non-human primates. Their approach could be used to target lots of different human diseases in many specific organs, they say, without delivering pizzas all over the body. Cell

The frontier spirit persists

Social scientists speak of a “causal effect of place,” which describes how the place where you grow up influences things in your life like educational attainment and lifetime earned income. Two economists at Arizona State University and Colorado School of Mines are suggesting a further wrinkle in this effect by tying it to the rugged individualism of the American frontier. People who grew up in former frontier towns and places where the culture is strongly informed by the hard-knock life of days of yore have greater upward mobility and higher adult earnings, they say. PNAS

Shape shifting as a result of climate change

Ornithologists at Deakin University in Victoria, Australia, are predicting that climate change will increasingly drive a shape-shifting response to a warming planet in some species, and they say there are already numerous examples of temperature-driven body changes in certain animals, including birds, bats, and rodents. In ecology, a 150-year-old concept known as “Allen’s rule” states that animals in warmer climates have larger appendages like ears and beaks to facilitate more efficient cooling of their bodies. With global warming, Allen’s rule may be seen more and more, with animal morphologies shifting toward larger appendages, the scientists say. Trends in Ecology and Evolution

Sample thermal images of Darwin’s finches in the field. Functional Ecology

New mechanism (and targets) for male infertility

Fewer than a third of all infertile men are diagnosed with a definitive cause of their infertility, but a new study from University Hospital of Muenster, Germany, may soon change those statistics. Gathering samples from stem cell compartments in the testes of men with and without impaired sperm production, the researchers found major alterations between the two groups of men. RNA sequencing revealed infertile men have increased numbers of the most undifferentiated sperm progenitor cells and more expression of the transcription factor EGR4. The work uncovers “highly interesting” targets for probing, the researchers say: It could reveal some of the genetic causes of male infertility and suggest new ways to treat it. Cell Reports Medicine

Cradle-to-grave catalog of half a million intestinal cells

The convoluted, microbe-rich column that is the human intestinal tract is a dynamic landscape that is constantly changing from its earliest in utero development to the end of life. To explore how human cells in the gut respond to our functional needs and environmental exposures, scientists at the Wellcome Sanger Institute in the United Kingdom have developed a catalog of human gut cells across human life. They analyzed the RNA and surface receptors contained in 420,000 cells from five anatomical regions in the developing gut and 11 distinct regions in the pediatric and adult digestive tract. The data, they say, will provide new insights into the role of diverse gut epithelial, immunological, and nerve cells in human development, health, and disease. Nature

Rebuilding heart muscle with stem cells

When a heart attack deprives the organ of sufficient oxygen, its cells can die, weakening the tissue and leading to later heart failure. “Remuscularizing” heart tissue with stem cells is a promising therapy, if fraught—it works, but the new cells are often prone to irregular, arrythmic beating, which can itself be deadly. Now researchers at the University of Washington have shown that when pigs who receive transplanted cardiomyocytes derived from human stem cells are also treated with the commercially available anti-arrhythmia drugs amiodarone and ivabradine, they fare better, suggesting a path forward for stem cell heart therapy in people. Stem Cell Reports

Can manipulating brain proteins reduce tolerance to opioids?

Opioid drugs like morphine and oxycodone are highly effective at blunting severe pain in the short term, but as we know all too tragically, over time people can develop tolerance, blunting the pain-killing effects of the drugs and contributing to addiction and overdose. Now researchers at MIT have found that giving mice repeated injections of morphine increases the levels of the cytokine protein interleukin-33 (IL-33) in their brain as it raises their tolerance for the drug and blunts its ability to modulate severe pain. This suggests that inhibiting or knocking out IL-33 or its receptor in the spinal cord could increase the lasting analgesic effect of opioid drugs for chronic pain management—though it’s unclear how the addictiveness of these drugs would be impacted. Science Signaling