A newly designed AAV-rDNA vector for persistent therapy in genetic liver diseases

Adeno-associated virus (AAV) is widely used in gene therapy but has limited integration, reducing long-term transgene expression. We engineered an AAV-rDNA vector to enhance integration and tested it in HT1 and hemophilia B mouse models. AAV-rDNA achieved 10–30 times higher integration and functional expression than control vectors, rescuing disease at much lower doses and restoring normal liver function. Integration was site-specific within rDNA repeats, confirmed by sequencing. These findings demonstrate that AAV-rDNA vectors enable efficient, stable gene expression and represent a promising approach for treating genetic disorders requiring persistent correction.