Safety and efficacy analysis of in vivo lentiviral gene therapy in pre-clinical ARC syndrome models

No effective treatments are currently available. Gene therapy offers a potential approach by restoring the missing VPS33B protein in liver cells.

Here, we show that liver-targeted lentiviral gene therapy safely and effectively rescues key features of ARC syndrome in a mouse model following in vivo administration by intravenous injection, combined with transient liver macrophage depletion. To assess the treatment efficacy, disease severity is exacerbated by 0.25% cholic acid diet feeds. A liver-specific vector shows a favourable safety profile over a ubiquitous vector.