Genetically engineered B cells are being used for gene therapy

Until now, B cells have not received the same attention — in fact, genetically modified versions have not been tested in humans. This is partly because “engineering B cells is not that easy,” said Shane Lu, a professor at Virginia Tech who demonstrated in 2009 how to generate B cells that contain an extra gene.

This early work, done at the California Institute of Technology, explored whether cells could be directed to produce antibodies against HIV, possibly becoming a new form of vaccination.

While that idea didn’t work, now biotech companies like Immusoft, Be Biopharma, And the Walking fish cures They want to harness cells as molecular factories to treat serious rare diseases. “These cells are powerhouses for protein secretion, and that’s something they want to take advantage of,” Lu says.

Immusoft licensed Caltech technology and got early investment from Peter Thiel’s biotech fund, Breakout Labs. Company founder Matthew Schulz, a software developer, boldly predicted in 2015 that the experiment would start right away. However, the technology the company calls “immune system programming” wasn’t as straightforward as computer encryption.

Ainsworth says Immusoft first had to spend several years finding reliable ways to add genes to B cells. Instead of using viruses or gene editing to make genetic changes, the company is now using transposons — a molecule that likes to cut and paste bits of DNA.

It also took time to convince the Food and Drug Administration to allow the trial. This is because it is known that if the added DNA ends up near cancer-promoting genes, it can sometimes turn them on.

“The FDA is concerned if you do this in a B cell, could you get a case of leukemia? That’s something they’ll be watching closely,” says Paul Orchard, a physician at the University of Minnesota who will be recruiting patients and conducting the study.

B cell factories

The first human test can solve some open questions about technology. The first is whether the enhanced cells would take up a long-term residence within the human bone marrow, where B cells normally live. Theoretically, the cells could survive for decades – up to a patient’s entire life. Another question is whether they will make enough of the missing enzyme to help stop MPS, a progressive disease.

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