Lentiviral gene therapy has been used in academia and industry since the early 2000s to treat hundreds of patients in multiple clinical trials – including four clinical trials of AVROBIO’s investigational gene therapies in lysosomal disorders. We use lentiviral vectors to integrate the therapeutic gene into the patient’s own stem cells for several reasons:
- They have sizable cargo space, which allows us to insert even large therapeutic genes into the patient’s stem cells.
- They are capable of permanently integrating a therapeutic gene directly into the patient’s chromosomes.
- This means that when the original batch of genetically modified stem cells divide and proliferate into trillions of daughter cells, each is expected to carry the therapeutic gene and be capable of expressing the active protein the patient needs.
The process of integrating the therapeutic gene into the cells takes place in a manufacturing facility, rather than in the patient’s body. This approach is called ex vivo gene therapy.
Our lentiviral approach is designed to enable treated stem cells to differentiate into many different cell types – including T cells, B cells and monocytes, each of which is expected to carry the therapeutic gene. Monocytes when they enter tissues become macrophages and in the central nervous system (CNS) they become microglia. Monocytes, macrophages and microglia carrying the therapeutic gene are understood to have the ability to traverse the blood-brain barrier and enter the CNS. We believe that once dispersed in the brain and CNS, these therapeutic cells may be able to slow, halt or even prevent disease progression in the CNS.
It’s important to note that our therapies are still investigational; they have not been approved by any regulatory body.
Learn more about AVROBIO’s personalized conditioning regimen.