Rodriques lab

Applied Biotechnology Laboratory

: Viral vectors

Introduction

Many of the most promising first-in-class therapies to be approved recently are in vivo gene therapies, in which genetic material is delivered to a living patient using engineered viruses.

This includes Zolgensma and Luxturna, both single-use treatments for spinal muscular atrophy and Leber’s congenital amaurosis, respectively. A diverse array of startups and therapeutics companies, such as Voyager Therapeutics and Encoded Therapeutics, are developing similar gene therapies for brain disorders. There is a widespread belief that the next ten years will see the approval of many more of these revolutionary in vivo gene therapies.

However, adeno-associated viruses (AAVs), the vectors commonly used in gene therapies such as Zolgensma and Luxturna, suffer from major drawbacks, including the presence of neutralizing antibodies in a large fraction of patients; a high cost of production; a small packaging capacity; liver toxicity; and an inability to cross the blood-brain barrier.

Moreover, gene expression from AAVs is in principle permanent, and may have damaging side-effects over long timescales. We are working to engineer novel viral vectors with larger packaging capsids, a wider range of patient applicability, and new integrated safety features, to enable the next generation of gene therapies.