The plato® platform includes:
A lentiviral vector and proprietary tags designed to optimize vector copy number, transduction efficiency and resulting enzyme/protein activity in target cells.
Advanced cryopreservation to extend shelf life and enable flexible scheduling for patients and healthcare providers.
A personalized conditioning regimen with precision dosing of busulfan, an established conditioning agent that we believe is key to the "head-to-toe" benefits we hope to demonstrate in our therapies.
An automated, closed manufacturing process intended to improve consistency and predictability of the drug product.
The system is self-contained and compact, which we believe will facilitate expansion of global manufacturing sites.
The technologies and processes that form plato are intended to be replicable across programs to accelerate overall pipeline development.
Hematopoietic stem cell (HSC) gene therapy using a lentiviral vector has been studied in academia and industry since the early 2000s to treat hundreds of patients in multiple clinical trials – including AVROBIO’s clinical trials for its investigational gene therapies in lysosomal disorders.
We use lentiviral vectors to attempt to permanently integrate the missing functional gene into the patient’s own HSCs. 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 inserted DNA and be capable of expressing the therapeutic protein the patient needs. The process of integrating the functional 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 approach is designed to enable genetically modified stem cells to differentiate into many different cell types – including T cells, B cells and monocytes, each of which is expected to carry the functional gene. Monocytes when they enter tissues become macrophages and in the central nervous system (CNS) they become microglia. Monocytes, macrophages and microglia carrying the functional 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 genetically modified cells express the needed therapeutic protein that may be able to slow, halt or even prevent disease throughout the body, including the brain and other hard-to-reach tissues.
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.
In some contexts, such as our programs in Pompe disease and Hunter syndrome, we use proprietary “tagging” technology to enhance the uptake of the therapeutic protein into target tissues, including CNS.
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