Scientists are recognizing the power of transmogrifying cells to do their bidding. Heck, we recently found that heart cells can be reprogrammed into “pacemaker cells” through gene therapy. But it can still be a quandary to figure out an efficient way of inserting the necessary transformative materials into the cell.
Cambridge startup SQZ Biotech has a slick, vector-free method of introducing stuff into cells, squeezing them in high-pressure tubules to loosen cell membrane pores so they’ll accept the alien materials. The process is performed on microfluidic chips – or, in common parlance, they’re another form of the ever-sexy lab-on-a-chip.
With its proprietary “CellSqueeze” process, a bunch of different kinds of material can be effectively inserted into cells – proteins, nanomaterials, antibodies, RNA and DNA. This novel method is being recognized across academia as a promising alternative to more traditional methods like electroporation and cell penetrating peptides.
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CellSqueeze says it produced a 10- to 100-fold improvement over these methods when it came to delivering transcription factors for stem cell reprogramming. The high-throughput platform can treat up to 100,000 cells per second, the company said.
SQZ Biotech’s technology comes from a crack team of MIT engineers. The company, funded largely by the NIH, the MIT-Portugal Program and the Kotch Institute Frontier Research Program, has been selling CellSqueeze kits since early last year.
Rather than using vectors to deliver material into cells, SQZ Biotech’s microfluidic chips have parallel channels that narrow to a kind of choke point that’s smaller than a cell’s diameter.
Cells are pushed through these mini tubules with pressure, and get “squeezed,” which opens up pores in the cell membrane – and voilà! Materials are diffused into the cell’s cytoplasm. Once they make it through the constriction, they bounce back to normal, pores sealed up.
The company built a simple animation that does a nice job of describing the process:
The key parameter for CellSqueeze is pressure – “the higher the pressure, the harsher the squeezing.” That means that although more material can be inserted into the cells, the viability of the cells decreases. So it’s a delicate dance that will likely require some trial and error on the researcher’s part (kind of standard, no?) to determine the best way to get foreign materials into the cell.
The pressure method is non-toxic to cells – an improvement over the oft-used viral vectors, electric shock and chemical agents that can kill cells and injure the inserted materials. SQZBiotech has tested this process on an array of cells – mouse and human immune cells like B cells and T cells, stem cells and fibroblasts, dendritic cells, and cells like HeLa and PANC-1.
