Our ApproachThe plato® Platform

ONE PLATFORM designed for state-of-the-art gene therapy

We have spent years optimizing the elements of plato®, our proprietary platform designed to bring gene therapy to patients worldwide. Plato has been developed with the goal of optimizing the safety, potency and durability of AVROBIO's investigational lentiviral gene therapies.

What is plato®?

The plato® platform includes:

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A lentiviral vector and proprietary tags designed to optimize vector copy number, transduction efficiency and resulting enzyme/protein activity in target cells.

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Advanced cryopreservation to extend shelf life and enable flexible scheduling for patients and healthcare providers.

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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.

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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.

Why lentiviral vectors?

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.

A closer look at conditioning

Conditioning is an essential step to optimize treatment. It’s used to prepare the patient’s body to receive the gene therapy. Conditioning helps the stem cells carrying the therapeutic gene to engraft in the patient’s bone marrow, where they will divide and proliferate into trillions of daughter cells. Each of those cells is expected to carry the therapeutic gene and be capable of expressing the active protein the patient needs throughout the body and brain. This engraftment is crucial for the gene therapy to be successful.

We currently use a medication called busulfan to enable a personalized conditioning regime with precision dosing. Busulfan is a clinically validated conditioning agent that has been used, both in academia and industry, as a single agent in a single cycle for hundreds of patients treated with investigational lentiviral gene therapies.

The conditioning process is associated with known side effects and does have risks. For instance, patients are more vulnerable to infection and bleeding for several weeks after conditioning. They may experience transient side effects such as fatigue, nausea, hair loss and mouth sores. There may be long-term risks to fertility; individuals undergoing conditioning may be advised to freeze their eggs or sperm in advance of the treatment.

We deploy a personalized medicine approach involving daily blood monitoring to assess the rate of busulfan metabolism and precisely adjust the next day’s dose accordingly. This process potentially allows us to maximize the effectiveness of conditioning — and the likelihood of successful engraftment — while minimizing the side effects.

At AVROBIO, we are committed to a process where each patient receives a personalized therapeutic approach and we are excited to have the opportunity to be a leader in this next frontier for lentiviral gene therapy.

Learn more about our commitment to individuals living with genetic disorders.


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Patients and Families

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Our Approach

Learn more about our personalized approach to gene therapy.