Klavs Jensen spent years in his lab at the Massachusetts Institute of Technology trying to find a better way to get stuff into cells without killing them. He’d stab them with needles, then teach a robot to do the same thing. A few years back, he started trying to shoot them with a jet of water. But cells are squishy things. Often, their exterior membranes wouldn’t rupture. They were hard to hold steady. The process was slow, and many cells would simply die.
“It wasn’t behaving properly. The results weren’t what we’d expect,” said Armon Sharei, who had begun working in Jensen’s lab as a doctoral student.
Then they tried a whole new approach. Instead of shooting the cells with a water jet, they bathed them in a solution of biological materials and gave them a squeeze. As it turns out, the cells behaved like a bunch of tiny sponges, soaking up large molecules, such as proteins and DNA.
Today, Jensen, Sharei, and several other researchers from their laboratory have amped up their operations and are developing a simple tool that researchers — and, ultimately, practicing physicians — could use to conduct lab work on the cheap. Their company, SQZ Biotech (pronounced “squeeze”), has created a system called the CellSqueeze platform. It pumps up to 1,000,000 cells per second through a system of channels that squeezes them, opening a bunch of small pores that allow foreign molecules to enter.
For decades, scientists have had only a few options for getting new genetic material or small particles, such as drugs, into cells. Sometimes, they use chemicals that a cell recognizes and welcomes to sneak other material across the cell’s exterior membrane. Other methods, like shocking a vial of cells with electricity to jolt them open, can speed up the process, but they stress the cells and end up killing large numbers of them.
By one measure, SQZ’s early research shows squeezing cells to be 10 to 100 times as effective as the existing methods.
“This opened up a lot of opportunities for us because, number one, it creates a lot less stress, and number two, you can add a lot of genes,” said Alpdogan Kantarci, a dental researcher and clinician at the Forsyth Institute in Cambridge who is testing a CellSqueeze device. Kantarci conducts research with immune cells, and he said squeezing the cells instead of zapping them doubled their survival rate, from around 35 percent to 70 percent.
CellSqueeze is a devilishly simple system. At its core is a silicon chip about the size of a child’s pinky with dozens of channels etched into its surface. The chip, whose surfaced is sealed with Pyrex glass, is placed between two small input and output tanks. The whole thing is driven by a tank of pressured nitrogen gas, something any lab will have.
The CellSqueeze’s mode of action is still sort of hypothetical, its creators acknowledge. Although they can tell when particles get into cells they run through the system — and when the holes in the cells seem to heal up — they haven’t actually seen the pores, or tears, or whatever they are. Still, for a company founded in 2013, they’re off to a good start. With more than a dozen full- and part-time employees and $1.7 million raised, they’ve expanded from a small space in the Seaport District to lab space at the University of Massachusetts Boston and manufacturing space in Woburn.
SQZ has big hopes for its device, which is being tested by about 40 researchers and a handful of private companies. A huge amount of lab work involves adding or removing genes from mice to make them develop differently, and that genetic modification could be done a lot faster.
In the longer run, Sharei said, CellSqueeze could be used in a therapeutic setting — say, by squeezing cancer-related proteins into human cells to teach people’s immune systems what to attack. Tests are not being done on humans yet. But if medical tests were to show success, CellSqueeze therapies could be done much more cheaply than other new anticancer treatments that involve changing the genes of individual cells, like CAR T cell therapy, Sharei said.
“If you could engineer these immune cells, you could really have big payoffs,” he said. “Ten, 15 years down the line, once we’ve been able to prove this in clinical trials, I’d like to see this in even a doctor’s office setting.”
Engineering cells by squeezing them
The CellSqueeze chip and a description on how it works:
James Abundis/Globe Staff