Ä¢¹½ÊÓƵAPP

While cell transplants made from a patient’s own cells, or delivered between identical twins, can maintain peace with the immune system, the customized nature of these treatments limits their applicability and attractiveness as therapeutic products. A universal cell—one that could be transplanted into anyone, without risk of immune rejection—is the innovation that many in the field have come to see as key to unleashing the full power of cell therapy. Rubius Therapeutics, a Ä¢¹½ÊÓƵAPP company launched in 2014, is founded on the premise that the body’s own red blood cells (RBCs) perfectly meet the same need.

RBCs are by far the most frequently transplanted tissue in medicine and, if sourced from a universal donor, can be given to any patient without the need for immunosuppression because the body does not see them as intruders. However, the unique biology of these cells presents its own challenges. RBCs lack a nucleus and the protein production equipment found in most other cells, which means biologists cannot use standard molecular tools to compel them to churn out a therapeutic protein. While some researchers have tried to get around this by loading RBCs with medicines, the process is inefficient and shortens the cell’s life span.

Rubius takes a different approach, building on work that its partners at MIT’s Lodish Lab have done to determine the sequence of molecular factors needed to coax fully equipped precursor cells into becoming red blood cells. Armed with this knowledge, researchers at Rubius are now able to add one or more therapeutic genes to the precursor cells and then wait for those cells to use the gene to make a protein. The modified cells expel their nucleus and the modified gene as they develop, but they retain their cargo of therapeutic proteins.

The result is a highly efficient and broadly applicable system with the potential to deliver therapeutic agents throughout the body for several months. Rubius’ Red Cell Therapeutics™ cells can carry their payloads internally, hiding proteins that might otherwise draw the ire of the immune system. The therapeutic action—say, the enzymatic breakdown of a toxic buildup in patients with phenylketonuria (PKU)—can take place inside the cell itself. Alternatively, the beneficial protein can be carried on the cell surface, where it can interact with other cells in the body.

Again, red blood cells can’t pump out proteins. So medicines that have to be released into the body call for cells with a different set of capabilities. This in turn speaks to another avenue of innovation—namely, the idea of creating ‘packages’ of living cells that not only are able to secrete specific proteins at therapeutic concentrations but can do so while remaining shielded from the immune system.

Ä¢¹½ÊÓƵAPP company Sigilon Therapeutics has spent the past few years since its founding in 2016 refining a technology platform with this objective in mind. Sigilon’s approach involves packing protein-producing cells into a small capsule that allows the free entry of oxygen and nutrients and the outward flow of therapeutic compounds. At the same time, the capsule prevents the body’s immune system from attacking the transplanted cells. Past attempts to create systems of this kind have been stymied by the tendency of the immune system to attack the capsule itself, resulting in scar tissue that effectively neutralizes the implant and chokes the living cells inside.