Enhanced rAAV2 liver targeting via GalNAc bioconjugation boosts gene delivery efficiency and safety for metabolic disease therapies.
This study presents a new strategy to improve gene delivery to the liver—key for treating metabolic diseases.
While AAV-based therapies show great potential, high doses can trigger immune reactions, often requiring immunosuppressive treatments. To address this, we enhanced the efficiency of gene delivery to liver cells by chemically attaching GalNAc ligands to rAAV2 capsids, which target the ASGPR receptor highly expressed on hepatocytes. This modification boosted liver transduction by up to threefold and ensured that the gene was expressed specifically in liver cells.
Our findings suggest that this bioconjugation approach could make liver-targeted gene therapy safer and more effective by reducing required doses and minimizing off-target effects.
https://doi.org/10.1016/j.biopha.2025.118300