3 Questions: Cullen Buie on a new era for cell

Genetic engineering and customized cell therapies might remodel well being care. In recent times, stem cells and gene-editing instruments like CRISPR have been making headlines for the chances they provide to deal with ailments, together with most cancers. However engineering cells is a sluggish, labor-intensive course of, making it troublesome to provide customized therapies at scale.

The startup Kytopen, co-founded by MIT Affiliate Professor Cullen Buie and former MIT postdoc and analysis scientist Paolo Garcia, gives an answer that might result in the mass manufacturing of genetically engineered cells. Right here, Buie solutions some questions on how Kytopen has grown since its founding.

Q: How did you and Paolo Garcia provide you with the unique concept for Kytopen?

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A: In some ways, the genesis of Kytopen began in 2013. After attending a convention on artificial biology, I acquired a DARPA Younger College Award to take a look at the issue of getting genetic materials into bacterial cells. That funding allowed me to rent Paulo Garcia as a postdoc. Two years later, we participated within the NSF Innovation Corps program, which helps researchers translate their applied sciences to purposes past the lab. By means of that program, we interviewed over 100 individuals in business and uncovered an enormous downside in genetic engineering: the supply of genetic materials to cells was too sluggish, too guide, and low throughput.

I keep in mind we visited one artificial biology firm that was attempting to automate the method. Every part was automated besides the precise gene supply step. For that half, two workers scientists would take 96 properly plates off the road and manually pipette materials into the cell samples, one-by-one, then carry out electroporation. We instantly recognized this as the issue space we needed to unravel and raised extra analysis funding to develop a brand new expertise that in the end led to Kytopen.

Q: Kytopen pivoted from specializing in bacterial cells to human cells. What impressed that change?

A: After we based the corporate in 2017 and have been conducting market analysis, researchers at firms would repeatedly ask, “Hey, have you ever ever considered utilizing this on mammalian cells or T cells or stem cells?” While you hear that a few times, you’re taking observe. We in all probability heard it 30 instances. We acknowledged there was much more worth to be made in that area. There’s a complete business that’s rising and being developed wherein clinicians want to take your cells and re-engineer them to combat your illness. They require related applied sciences as what we have been creating for micro organism — in addition they wanted them to be excessive throughput and produced at massive volumes. Across the identical time, we acquired seed funding from The Engine. That gave us the sources wanted to discover this area. As soon as we discovered this potential utility in human immune cells, we employed a number of immunologists to assist us adapt the expertise from engaged on micro organism to engaged on human cells.

Q: Are you able to clarify how Kytopen’s expertise really works?

A: The expertise we invented at Kytopen, known as Flowfect, makes use of electrical fields and a steady fluid movement on the identical time to open pores in cells and ship genetic supplies, like mRNA and DNA. Utilizing microfluidic gadgets, we’re making use of an electrical subject whereas flowing at very excessive movement charges. The excessive movement charges impose shear stress on the cells that, coupled with the electrical subject, permits you to open pores. We use a lot much less electrical power than you usually would wish for electroporation because of this mechanical side. Because it seems for a lot of completely different cell sorts, this results in higher bodily outcomes for the cells. They reply higher to this mix of mechanical and electrical stress, as a result of we don’t must shock them as a lot as conventional electroporation. As a result of we’re utilizing these very quick flows to induce mechanical pressure on the cell, the method is excessive throughput. We’re flowing at very excessive movement charges, which suggests we are able to course of a variety of cells. Flowfect permits us to course of billions of cells per minute. That is essential for lots of the therapies being developed, which want round one million cells per kilogram of the affected person. This opens up a world of prospects for secure immunotherapies, together with immuno-oncology and gene-editing purposes.


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