Non-viral gene transfer for rare diseases

X M Anguela(1)

1: Asklepios Biopharmaceutical

In vivo clinical investigation using non-viral vectors has mostly coalesced around treatment of cancer and as a vaccination tool. This is in part due to two main characteristics of non-viral vectors: short-lived transgene expression and their ability to elicit a strong immune response against the encoded protein combined with generation of an immunogenic milieu around the site of injection. However, for treatment of rare diseases, immunologically silent and long-lasting transgene expression is typically sought after. As such, viral vectors are currently the preferred choice as gene transfer tools for the treatment of rare, monogenic indications.
However, recent developments in the field of non-viral gene transfer are starting to broaden the therapeutic potential of such vectors. In this talk, we will summarize some of the latest developments in non-viral gene transfer tools for the treatment of rare disease. We will place special emphasis on the use of lipid nanoparticles containing RNA for the treatment of monogenic diseases, both in the context of standalone therapies and also in combination with viral vectors to mediate genome editing. We will also discuss the potential use of RNA- only vectors currently under preclinical development that might one day, if successful, circumvent the need for DNA-based viral vectors to achieve long-lasting expression in vivo.