ArticleMolecular therapy. Advances2026
Whole-brain biodistribution of AAV2, AAV8, and AAV-B10 after unilateral intracerebroventricular injection.
Article in Molecular therapy. Advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Adeno-associated virus (AAV) vectors represent promising tools for central nervous system (CNS) gene therapy; however, achieving efficient and widespread brain gene distribution while minimizing peripheral off-target exposure remains challenging. This study compares the brain and peripheral biodistribution patterns of three AAV serotypes, AAV2, AAV8, and AAV-B10, following intracerebroventricular (i.c.v.) administration in adult female mice. Using advanced tissue clearing methods with high-resolution light-sheet fluorescence microscopy, we visualized whole-brain AAV enhanced green fluorescent protein (eGFP) reporter distribution at single-cell resolution and employed semi-automated spatial quantification to analyze regional eGFP reporter signal. Each vector carried identical eGFP expression cassettes under the ubiquitous CAG promoter. AAV-B10 demonstrated superior parenchymal eGFP signal across multiple brain regions, with significantly higher expression in the cortex, midbrain, striatum, and thalamus compared to other serotypes. In contrast, AAV2 exhibited distinctive tropism for ventricular structures, with robust eGFP signal of ependymal cells lining the ventricular walls and choroid plexus. AAV8 showed intermediate eGFP distribution targeting the choroid plexus epithelium. Following i.c.v. administration, peripheral leakage of AAV genomes was observed, with AAV8 showing strong liver enrichment of eGFP transgene and AAV-B10 displaying broader yet weaker distribution across peripheral tissues. These serotype-specific distribution profiles provide critical insights for optimizing vector selection based on therapeutic requirements and target regions, potentially enhancing the efficacy of AAV-based gene therapies for neurological disorders.
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