Our cells are packed with unrealized potential. Almost every human cell contains the genetic information it needs to become any other kind of cell. A skin cell, for example, has the same genes as a muscle cell or a brain neuron, but in each type of cell only some of those genes are switched on, while others remain silent. It’s a little like making different meals out of the same ingredients cupboard. If we understand the recipe behind each type of cell, then theoretically we can use this information to engineer every single cell type in the human body.
That is Mark Kotter’s goal. Kotter is the CEO and cofounder of bit.bio—a Cambridge, UK, based company that wants to revolutionize clinical research and drug discovery by producing precisely engineered batches of human cells. Basic scientific research into new drugs and treatments often starts with tests in mice, or in the most widely used human cell lines: kidney cells and cervical cancer cells. This can be a problem, because the cells being experimented on may have major differences to the cells that a candidate drug is supposed to target in the human body. A drug that works in a mouse may turn out not to work when it’s tested in humans. “There is no mouse on this planet that has ever suffered from Alzheimer’s, it just doesn’t exist,” Kotter says. But testing a potential Alzheimer’s drug on a human brain cell engineered to have signs of Alzheimer’s disease could give a much clearer indication of whether that drug is likely to be successful.
“Every cell type has its own little program, or postcode—a combination of transcription factors that defines it,” says Kotter. By inserting the right program into a stem cell, researchers can activate genes that code for these transcription factors and turn a stem cell into a specific type of mature cell. Unfortunately, biology has a way of fighting back. Cells often silence these genes, stopping the transcription factors from being produced. Kotter’s solution—discovered as part of his research at the University of Cambridge—is to insert this program in a region of the genome that’s protected against gene silencing, something Kotter refers to as a “genetic safe harbor.”
Bit.bio currently sells two different reprogrammed cell lines: muscle cells and a specific kind of brain neuron, but the plan is to create bespoke cell lines for use in the pharmaceutical industry and academic research. “What we’re doing with our partners in the industry now is to create genetic modifications that are relevant for diseases,” Kotter says. He compares this approach to running software on a computer. By inserting the right bit of code into a cell’s genome, you can control how that cell behaves. “That means that we can now run programs, and we can reprogram human cells,” Kotter says. The cell reprogramming technology could also go well beyond model cell lines and help develop whole new kinds of treatment, such as cell therapy.
In some cell therapies, a patient’s own immune cells are grown outside of their body before being modified and inserted back into it to help fight a disease—a long and expensive process. One kind of cell therapy used to treat young people with leukemia costs more than £280,000 ($371,400) per patient. Bit.bio’s chief medical officer Ramy Ibrahim says that the firm’s technology could help drive down the cost of cell therapy and make it easier to manufacture immune cells at a large scale. “Having abundant numbers of the right cell types that we can now make edits to, I think will be transformational,” he says.
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