A team led by bioengineers at the University of California San Diego has developed a genome-scale reference map that details how individual genes control the functions and identities of human stem cells.

MIT engineers have developed a noninvasive pacemaker that stimulates the heart using ultrasound. The design could one day provide a surgery-free alternative to traditional cardiac implants.

The new device is designed as a small sticker that can be worn on the chest. Tiny transducers on the sticker send ultrasound pulses through the chest to stimulate the heart. The ultrasound waves trigger the opening of certain ion channels in heart cells, an effect the researchers amplified through genetic engineering. When the channels open, they let in calcium, which signals a heart cell to squeeze and beat.

In experiments in the lab, the researchers applied ultrasound waves to engineered human cardiac cells and found that the pulses effectively maintained the cells’ healthy contractions. They also tested the ultrasound sticker on rats and found the device quickly, safely, and noninvasively corrected arrhythmias and restored normal, regular heart contractions.

But there are other possible CAR T risks for autoimmune patients. In February, FDA officials published a paper endorsing CAR T’s potential in autoimmunity but warning of “unpredictable long-term toxicity.” CAR T treatment for cancer, the authors noted, has been linked to diverse long-term issues such as Parkinson’s disease. There have also been cases in which the bioengineered cells themselves turned malignant, causing new, T cell-based cancers.

Causing a secondary cancer may be an acceptable risk when treating a life-threatening cancer, but probably not for autoimmunity, says Matt Lunning, medical director for gene and cellular therapy at Nebraska Medicine, in Omaha. How to balance the risk between the impacts of an autoimmune disease, which can range widely in severity, and the difficult-to-quantify risk of future side effects or cancers remains a major open question.

Researchers are already working on second-and third-generation versions of CAR T that they expect to be safer for both cancer and autoimmunity. For example, James Howard, a neuromuscular neurologist at the University of North Carolina at Chapel Hill, is testing a technology from a company called Cartesian Therapeutics that encodes the CAR using molecules of mRNA, the short-lived genetic messenger used in Covid-19 vaccines, instead of long-lasting DNA. The CAR T cells should wipe out B cells for only as long as the mRNA persists, then lose their B cell-targeting abilities. With no chance for genetically modified T cells to hang around long-term, there should be no cancer risk.