Tech

Genetically engineered B cells are being used for gene therapy


To date, B cells have not received such attention — indeed, the genetically engineered versions have never been tested in humans. That’s partly because “B-cell engineering isn’t so easy,” said Xin Luo, a professor at Virginia Tech who demonstrated how to make B cells with the extra gene in 2009.

That early work, done at Caltech, investigated whether cells could be directed to make antibodies against HIV, perhaps becoming a new form of vaccination.

Although that idea didn’t work out, now biotech companies like Immusoft, Be Biopharma, and Walking Fish Therapy wants to harness cells as a molecular factory to treat rare and fatal diseases. “These cells are the energy source to secrete protein, so that’s what they want to take advantage of,” says Luo.

Immusoft licensed Caltech technology and received an early investment from Peter Thiel Biotechnology Foundation, Breakout Labs. Company founder Matthew Scholz, a software developer, boldly predicted in 2015 that an experiment could begin immediately. However, the technology, which the company calls “programming the immune system,” turns out to be not as simple as coding a computer.

Ainsworth says Immusoft first spent several years finding reliable ways to add genes to B cells. Instead of using viruses or gene editing to make genetic changes, the company now uses uses a transposon – a molecule that likes to cut and paste fragments of DNA.

It also took time to convince the FDA to allow the test. That’s because it’s known that if the added DNA ends up near genes that promote cancer, it can sometimes turn them on.

“The FDA is concerned if you do this in B cells, will you develop the leukemia condition? That’s something they’ll be watching pretty closely,” said Paul Orchard, a doctor at the University of Minnesota who will be recruiting patients and conducting the study.

B cell factory

The first human trial could solve some open questions about the technology. One is whether the enhancer cells have a permanent residence inside the human bone marrow, where B cells normally live. In theory, cells could last for decades – even the entire life of a patient. Another question is whether they make enough of the missing enzyme to help stop MPS, a progressive disease.



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