Adeno-associated virus type 4 (AAV4) targets ependyma and astrocytes in the subventricular zone and RMS

Abstract

The subventricular zone (SVZ) is one of the neurogenic niches in the adult mammalian brain. The SVZ is of interest for studies on neurogenesis and stem cell therapy. Here, we report specific transduction of ependyma and/or astrocytes by recombinant adeno-associated virus type 4 (AAV4) viral vectors. AAV4 vectors encoding b-galactosidase or eGFP were injected into the lateral ventricles of neonatal and adult C57BL/6 mouse brains. In addition, SVZ injections were conducted on adult mice. AAV4 vectors show a characteristic transduction of the ependyma independent of delivery route. However, AAV4 virus injected into the SVZ targeted GFAP positive astrocytes forming the glial tube in the SVZ and rostral migratory stream (RMS). Our results introduce AAV4 as a new tool by which to manipulate glial cells in the RMS. Gene Therapy (2005) 12, 1503-1508.

Functional Correction of CNS Phenotypes in a Lysosomal Storage Disease Model Using Adeno-Associated Virus Type 4 Vectors

“…A second possibility for the elevated ␤-glucuronidase activity in the RMS would be direct transduction of neuroblasts or progenitor cells in the SVZ. This is unlikely, however, because intraventricular injection of AAV4 exclusively transduces ependyma and not neuroblasts or SVZ progenitors (Liu et al, 2005).…”

“…As such, ependymal cells provide a cellular depot for secretion of enzymes into the CSF, including ␤-glucuronidase (Ghodsi et al, 1999). In this study, we used adeno-associated virus type 4 (AAV4), which transduces the ependyma with high efficiency (Davidson et al, 2000;Liu et al, 2005), to test whether constitutive secretion of ␤-glucuronidase into CSF could reverse existing lysosomal pathology and behavioral deficits in the MPS VII mouse model.…”

Suppression of tissue inhibitor of metalloproteinase-1 by recombinant adeno-associated viruses carrying siRNAs in hepatic stellate cells

“…These investigations provided much of the safety profile of the vector and experience in human applications, paving the way for subsequent administration to other disorders such as hemophilia (13,14), retinal diseases (15,16), muscular dystrophy (17,18), neurological diseases (19,20) or cancer (21,22). Our results suggest that AAV vectors also have the potential for the therapeutic delivery of siRNA.…”

RNAi: a potential therapy for the dominantly inherited nucleotide repeat diseases

“…While the distribution of vector often improves with increasing titer, some serotypes diffuse further from the injection site than others, 56,57 or transduce nonneuronal cells. 56,58 Results to date…”