Gene Therapy for Heart Arrhythmias

One possible treatment option for cardiac arrhythmias are approaches that enhance electrical excitability and action potential conduction in the heart. One way this could be done is by stably overexpressing mammalian voltage-gated sodium channels. However, the channels’ large size precludes delivery via viral vectors. Now, researchers have demonstrated a gene therapy that helps heart muscle cells electrically activate in live mice. The first demonstration of its kind, the approach features engineered bacterial genes that code for sodium ion channels and could lead to therapies to treat a wide variety of electrical heart diseases and disorders.

This detailed image of a single mouse heart muscle cell shows its cell membrane expressing the new sodium ion channel genes (magenta) after researchers delivered the therapy through an injection into the mouse veins

We were able to improve how well heart muscle cells can initiate and spread electrical activity, which is hard to accomplish with drugs or other tools,” said Nenad Bursac, PhD, professor of biomedical engineering at Duke University. “The method we used to deliver genes in heart muscle cells of mice has been previously shown to persist for a long time, which means it could effectively help hearts that struggle to beat as regularly as they should.”

The platform“utilizes small-size, codon-optimized engineered prokaryotic sodium channels (BacNav) driven by muscle-specific promoters that significantly enhance excitability and conduction in rat and human cardiomyocytes in vitro and adult cardiac tissues from multiple species in silico.”

Several years ago, members of the lab mutated bacterial genes so that the channels they encode could become active in human cells. In this new work, Tianyu Wu, doctoral student, further optimized the content of the genes and combined them with a promoter that exclusively restricts channel production to heart muscle cells.

We worked to find where the sodium ion channels were actually formed, and, as we hoped, we found that they only went into the working muscle cells of the heart within the atria and ventricles,” Wu said. “We also found that they did not end up in the heart cells that originate the heartbeat, which we also wanted to avoid.”

As a proof of concept, tests on cells suggested that the treatment improves electrical excitability enough to prevent human abnormalities like arrhythmias. More specifically, the work showed that “the expression of BacNav significantly reduces occurrence of conduction block and reentrant arrhythmias in fibrotic cardiac cultures.

The work is published in Nature Communications, in the paper, Engineered bacterial voltage-gated sodium channel platform for cardiac gene therapy.”

Source: https://pratt.duke.edu/
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Sodium Batteries May Power New Electric Cars

Half a century ago, the battery of the future was built out of sodium. The reason has to do with why the seas are salty. Sodium is a light element that ionizes easily, giving up one of its electrons. In a battery, those ions shuttle back and forth between two oppositely charged plates, generating a current. This looked like a promising way to power a house or a car. But then another element crashed the party: lithium, sodium’s upstairs neighbor on the periodic table. In 1991, Sony commercialized the first rechargeable lithium-ion battery, which was small and portable enough to power its handheld video cameras. Lithium was lighter and easier to work with than sodium, and so a battery industry grew up around it. Companies and research labs raced to pack more energy into less space. Sodium faded into the background.

So it was surprising this summer when China’s CATL, one of the world’s largest battery makers, announced sodium would play a role in the electrified future. CATL, like its competitors, is a lithium company through and through. But starting in 2023, it will begin placing sodium cells alongside lithium ones inside the battery packs that power electric cars. Why? Well, for one thing, a CATL executive pointed out that sodium is cheaper than lithium, and performs better in cold weather. But it was also hedging against an issue that was difficult to imagine in 1991. By the end of this decade, the world will be running short on the raw materials for batteries—not just lithium, but also metals like nickel and cobalt. Now that electrification is actually happening on a big scale, it’s time to think about diversifying. A CATL spokesperson said it started thinking about sodium 10 years ago.

CATL’s announcement “really injected new energy into the people who work on sodium,” says Shirley Meng, a battery scientist at the University of California, San Diego who works extensively with both elements. As a young professor, Meng started working with sodium in part because she was looking for a suitably weird niche to stand out in—but also because she believed it had potential. “The biggest barrier to success for sodium was that lithium was so successful,” she says.

Lithium is not exceptionally rare. But deposits are concentrated in places that are hard to mine. So companies like CATL compete to secure a slice of the supply from a limited number of mines, mostly located in Australia and the Andes. Meanwhile, reserves in North America are tied up in environmental disputes, raising concerns in the US about the security of the supply chains. Competition is even fiercer for nickel—which Elon Musk has called the “biggest concern” for the future of EV batteries, due to price and supply constraints—and for cobalt, 70 percent of which is dug up in the Democratic Republic of the Congo.

As more mines open, there will probably be enough lithium to power all the world’s vehicles, Meng says. But that doesn’t account for all of the things poised for electrification that aren’t cars: chiefly, the batteries that will manage the load within microgrids and keep our lights on at night when the rooftop solar panels are in the dark. Those are the kinds of applications Meng had in mind when she got into sodium research. “I was thinking everybody would have a refrigerator for electrons in your home in the same way you have a refrigerator for food,” she says. “I think that really is the vision for grid storage.

Source: https://www.wired.com/