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  • Title: Comparison of gene transfer to the murine liver following intraperitoneal and intraportal delivery of hepatotropic AAV pseudo-serotypes.
    Author: Dane AP, Wowro SJ, Cunningham SC, Alexander IE.
    Journal: Gene Ther; 2013 Apr; 20(4):460-4. PubMed ID: 22895507.
    Abstract:
    Adeno-associated virus (AAV) vectors are highly efficient for liver-targeted gene delivery in murine models and show promise in early phase human clinical trials. This efficiency is capsid-dependent and was only achieved after discovery that the AAV2 vector genome could be trans-encapsidated into the capsids of other AAV serotypes. This confers novel host-vector biology and target tissue tropism. Optimal exploitation of the growing number of AAV vector pseudo-serotypes, however, requires detailed context-dependent characterisation of transduction performance. In this study, we compared the pattern and efficiency of gene delivery to the adult mouse liver following intraportal and intraperitoneal injection of vectors pseudo-serotyped with known hepatotropic capsids from AAV type 7, 8, 9 and rhesus 10. Vectors pseudo-serotyped with these hepatotropic capsids proved relatively efficient irrespective of administration route, with higher transgene expression in males despite equivalent vector genome delivery in females. Transgene expression was predominantly centrilobular in contrast to the AAV2 capsid, which gave a periportal pattern of expression. Most intriguingly, vector genome performance appeared to be delivery route-dependent, consistent with the possibility of in vivo capsid modification. These data not only inform the experimental use of AAV vectors, but also provide insight into novel aspects of host-vector biology requiring further focused analysis.
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