Widespread dispersion of adeno-associated virus serotype 1 and adeno-associatedvirus serotype 6 vectors in the rat central nervous system and in human glioblastoma multiforme xenografts.
Journal Title: Human Gene Therapy - Year 2005, Vol 16, Issue 3
Abstract
The transduction patterns of recombinant adeno-associated virus serotype1 (AAV1) and serotype 6 (AAV6) vectors were assessed in human glioblastoma multiforme (GBM) cell lines,in human GBM biopsy spheroids, and in tumor xenografts growing in nude rat brains. All the cell linestested (A172, D37, GaMg, HF66, and U373Mg) were found to be permissive to both AAV1 and AAV6 vectors,and thus displayed a transduction pattern similar to AAV2 vectors. For every cell line tested, the transductionefficiency displayed by AAV2 vectors was better than by isogenic and isopromoter AAV1 vectors. Transductionefficiency was dependent on the viral particle number used, suggesting that the receptors for these vectorsare widely distributed in GBM tissues. Interestingly, AAV1, AAV2, and AAV6 vectors were able to infectand transduce the same cells when added simultaneously to monolayer cultures. Infection of human GBMbiopsy spheroids with AAV1 and AAV6 vectors resulted in transgene expression both at the surface layersand in the core of the spheroids. Following injection of AAV1 and AAV6 vectors into human GBM biopsyxenografts growing in nude rat brains, reporter gene expression was seen both in the periphery as wellas in the central regions of the tumors. When injected into the normal rat brain, both AAV1 and AAV6vectors were found to transduce several central nervous system (CNS) regions. The presented results suggesta potential therapeutic role for AAV1 and AAV6 vectors in gene therapy for GBM and also for other CNSmalignancies.
Authors and Affiliations
Peter C Huszthy, Agnete Svendsen, James M Wilson, Robert M Kotin, Rolf Bjerkvig, Frank Hoover
Keywords
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Widespread dispersion of adeno-associated virus serotype 1 and adeno-associatedvirus serotype 6 vectors in the rat central nervous system and in human glioblastoma multiforme xenografts.
The transduction patterns of recombinant adeno-associated virus serotype1 (AAV1) and serotype 6 (AAV6) vectors were assessed in human glioblastoma multiforme (GBM) cell lines,in human GBM biopsy spheroids, and in tumor x...