Breaching the blood-brain barrier: AAV triggers dose-dependent toxicity in the brain
Daniel Stone, Martine Aubert, Keith R. Jerome
Abstract
Since in vivo transduction of neurons and glia by adeno-associated virus (AAV) vectors was first demonstrated in rat brain,1 it has been shown that AAV can efficiently transduce neurons, microglia, astrocytes, and oligodendrocytes across multiple species, and AAV vectors have become a widely used tool in basic and therapeutic research targeting the nervous system.2 However, recent observations have shown that the administration of AAV vectors at high doses can cause local or widespread neurotoxicity in the central (CNS) and peripheral (PNS) nervous systems, and the long-term consequences of this for human therapies targeting nervous tissue remain to be determined.
Topics & Concepts
Central nervous systemNeurotoxicityMicrogliaAdeno-associated virusNeuroscienceIn vivoNervous systemGenetic enhancementBiologyMedicineImmunologyToxicityVector (molecular biology)Internal medicineGeneInflammationGeneticsRecombinant DNAVirus-based gene therapy researchNeurogenesis and neuroplasticity mechanismsRNA Interference and Gene Delivery