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The first gene therapies approved in the U.S. have undeniably transformed lives. Children who had been nearly blind can now see well enough to play with friends at dusk. Babies who would otherwise be paralyzed are crawling and learning to walk.

These gene therapies work by delivering a therapeutic gene encoding for functional protein to specific cell types, such as the retina or motor neurons. But what if the genetic disease affects every cell in a patient’s body? How do we impact all these cells?

One approach with growing evidence: Harnessing the power of stem cells.

The approach in question, known as ex vivo lentiviral gene therapy, has been used to treat hundreds of patients in clinical trials over more than a dozen years and has already demonstrated efficacy in several diseases. Especially notable: third party clinical data show that this approach may prevent and treat symptoms in both the brain and the body a rare feat.

Ex vivo lentiviral gene therapy starts with the patient’s own hematopoietic stem cells, collected from their blood. A lentiviral vector is used to ferry a therapeutic gene into each cell, where it’s integrated into the DNA. The treated cells are then reinfused into the patient. Over the following days, these cells are expected to settle back into their “home base” in the bone marrow and proliferate, asymetrically dividing to replenish themselves (which may give the therapy durability) as well as to produce billions and then trillions of daughter cells, each carrying the therapeutic gene.

This is where the power of hematopoietic stem cells comes in: Those daughter cells are expected to differentiate into all the components of the blood and immune system, including cell types called monocytes which are known to readily cross the blood-brain barrier and become microglia, which are distributed throughout the CNS.

“Developing therapies that can reach the entire body has been a huge challenge for decades. We now have emerging evidence of a potential solution — one that could lead to revolutionary new treatments,”


This incredible migration has been observed in the clinic: A 2020 publication documented the presence of functional donor macrophages (a cell type derived from monocytes) in the brains of patients who had received IV infusions of hematopoietic stem cells from donors. These patients had a genetic mutation that left them unable to produce an essential functional enzyme, but the normal donor cells expressed it not just in their body, but in their central nervous system, as well.

We believe the “head-to-toe” reach of ex vivo lentiviral therapy is particularly useful for diseases with devastating effects throughout the body. These include lysosomal disorders such as Fabry disease, Gaucher disease, Pompe disease, Hunter syndrome and cystinosis, each of which is caused by a single genetic mutation that leads to insufficient production of a functional protein needed for cells to work properly.

Without that protein, toxic substrates accumulate in the body and brain, causing complications that can range from kidney failure to excruciating bone pain to a progressive loss of muscle strength and cognitive function. The devastating nature of these symptoms has been thoroughly documented for decades.

“The cumulative buildup of toxic substrate causes relentless degeneration. In Hunter syndrome, for example, the progressive neurological damage can rob children of their ability to walk, talk and engage with the outside world,” says Prof. Bigger.

Ex vivo lentiviral gene therapy is designed to prevent, halt or even potentially reverse the full breadth of symptoms in the body and brain.

Indeed, we believe it holds the potential to deliver a functional cure in a single dose.

“Lentiviral gene therapy’s potential to address symptoms of both the peripheral tissues and the central nervous system is a dramatic leap forward for the treatment of these currently incurable disorders and a source of hope for families worldwide,” says Prof. Bigger.

AVROBIO’s vision is to bring personalized gene therapy to the world. By harnessing the power of the body’s own stem cells, we strive to transform the future for families living with lysosomal disorders.

To learn more about lentiviral gene therapy and its head-to-toe reach, please visit