Venturing beyond AAVs and LNPs to deliver therapeutic cargo

The ranks of companies developing non-viral drug delivery methods are swelling, even beyond traditional lipid nanoparticles. As vehicle formats proliferate, the goals largely remain the same: target select tissues outside the liver, reduce immunogenicity to enable repeat dosing, and increase the efficiency of payload delivery.

The handful of pioneering AAV gene therapies that have made it to market have opened a vast opportunity for using nucleic acid constructs to treat disease: from additional gene replacement therapies for rare genetic diseases to vectorized biologics for common chronic conditions. As pivotal as these first products have been, AAV vectors are beset with challenges. Among these is the fact that their viral nature causes an immune response that precludes administration of a second dose, and that makes dose-selection both more critical and more challenging than conventional therapies. ...