Efficient AAV8 delivery to the liver via isolated hepatic perfusion and analysis of hepatic lobule transduction patterns
Brief intro:
- Author: Chao Wang, Mingming Fan, Jianrong Liu, Xiaolu Guo, Zhipeng Tan, Xueying Huang, Zhuoran Li, Xiaomei Liu, Ye Zhang, Jianqi Feng, Rui Fang, Li Wang, Qiong Ke
- Journal: Liver Research
- Doi: https://www.doi.org/10.1016/j.livres.2025.04.006
- Publication Date: 2025 Apr 29
Abstract
Background and aims: Adeno-associated virus (AAV) is becoming an attractive vector due to its low toxicity and minimal immunogenicity. However, liver-targeted AAV gene therapy still faces challenges, such as low delivery efficiency and safety risks associated with high vector doses. Isolated hepatic perfusion (IHP) has been explored as a localized drug delivery method, yet its full potential in gene therapy remains under investigation. Here, we investigated the efficiency of AAV8 delivery via the IHP route and its preference for hepatic transduction. Methods: The IHP route was established through surgery in rats and cynomolgus monkey, and the AAV8-dTomato solution was injected into the entire liver through the inflow tract and maintained for 10 minutes. One week later, liver tissues were obtained, and the dTomato fluorescence expression area fraction and intensity were analyzed. Results: AAV8-dTomato delivery via the IHP resulted in over 60% dTomato-positive areas in rat liver and showed higher efficiency than the portal vein (PV) and inferior vena cava (IVC) routes at equivalent doses. In rats, AAV8-dTomato expression was primarily periportal across IHP, PV, and IVC routes, while in cynomolgus monkey, IHP delivery showed a pericentral pattern. Conclusions: In this study, we found that IHP is an effective strategy for AAV8 delivery. In addition, the distribution characteristics of AAV8, when delivered in cynomolgus monkey via IHP, provide candidate vector delivery schemes for gene therapy for different types of genetic liver diseases.
About PackGene
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
