The success of adeno-associated virus (AAV) vectors in delivering gene therapy is well-documented, but the use of lentiviral vectors in gene therapy may be particularly suited to a number of rare lysosomal disorders.

Geoff Mackay, president and CEO of Avrobio, spoke about the emerging technology on August 26, 2021, the second day of the 3-day World Orphan Drug Congress USA 2021 — an annual conference being held in person for the first time since 2019.

“The common thread in many of our lysosomal disorders is this need to impact both above the neck and below the neck. Certainly, the culprit is the blood-brain barrier,” he said. “Our goal is to free these patients from a lifetime of disease, and that’s what we set out to do.”

Mackay has 25 years of industry experience, including a decade with Novartis. He said that Avrobio, headquartered in Cambridge, Massachusetts, spent 5 years building up a lysosomal disorder pipeline based on lentiviral gene therapy.

“There’s a long road to go beyond this, and lentiviral gene therapies for lysosomal disorders are still investigational,” he said — particularly when it comes to genetic conditions such as Gaucher disease and Fabry disease.

“Before today’s standard of care arrived, these patients had very little opportunity. Enzyme replacement therapy has done an enormous good, and patients describe it as a godsend. But now we’ve started to ask: what else do we need to address?”

Lentiviral gene therapy involves the insertion, modification, or deletion of genes using the lentivirus family of viruses responsible for AIDS and other diseases. It has already been approved to treat beta thalassemia and metachromatic leukodystrophy (MLD), and its application is being investigated in at least a dozen other illnesses including Fabry, Gaucher type 1, Hunter disease, Sanfilippo syndrome, and sickle cell disease.

“The whole vision of our company is to untether patients from what’s an onerous standard of care: biweekly infusions of enzyme replacement therapy for a lifetime,” he said, estimating that costs for such therapy could reach $14 million over the life span of a patient with Fabry disease.

“But it’s more than that,” he said. “We want to halt disease progression instead of just slowing it down, and we want to get the enzyme to where it needs to be. Our hope is that this platform will one day allow us to develop a cost-effective approach.”


The importance of considering both the body and the mind in treating clinical manifestations of genetic disease. Presented at: World Orphan Drug Congress USA 2021: August 26, 2021; National Harbor, MD.