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Mol Ther. 2011 Nov;19(11):1990-8. doi: 10.1038/mt.2011.146. Epub 2011 Aug 9.

Intranasal administration of adeno-associated virus type 12 (AAV12) leads to transduction of the nasal epithelia and can initiate transgene-specific immune response.

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Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.


A critical aspect in defining the utility of a vector for gene therapy applications is the cell tropism and biodistribution of the vector. Adeno-associated virus type 12 (AAV12) has several unique biological and immunological properties that could be exploited for gene therapy purposes, including a unique cell surface receptor, transduction of epithelial cells, and limited neutralization by pooled human antibodies. However, little is known about its cell tropism and biodistribution in vivo. In vivo biodistribution studies with AAV12 vectors encoding a cytomegalovirus promoted luciferase transgene indicated preferential transduction of the nasal epithelia which was not observed with AAV2-based vectors. Expression peaked 2 weeks postadministration, before decreasing to a persistent level. The level of neutralizing antibodies (Nab) induced was sevenfold lower for AAV12 than for AAV2, an advantage for use in repeat administration. Furthermore, vectors encoding influenza A nucleoprotein (NP), an antigen which has previously been shown to induce immune protection against challenge, resulted in generation of both anti-A/NP antibodies and lung anti-A/NP T cells. Our findings suggest further evaluation of AAV12 as a vector for gene therapy and as a potential nasal vaccine.

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