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- W4318071669 abstract "Abstract A barrier to advancing engineered adeno-associated viral vectors (AAVs) for precision access to cell subtypes is a lack of high-throughput, high-resolution assays to characterize in vivo transduction profiles. In this study, we developed an ultrasensitive, sequential fluorescence in situ hybridization (USeqFISH) method for spatial transcriptomic profiling of endogenous and viral RNA with a short barcode in intact tissue volumes by integrating hydrogel-based tissue clearing, enhanced signal amplification and multiplexing using sequential labeling. Using USeqFISH, we investigated the transduction and cell subtype tropisms across mouse brain regions of six systemic AAVs, including AAV-PHP.AX, a new variant that transduces robustly and efficiently across neurons and astrocytes. Here we reveal distinct cell subtype biases of each AAV variant, including a bias of AAV-PHP.N toward excitatory neurons. USeqFISH also enables profiling of pooled regulatory cargos, as we show for a 13-variant pool of microRNA target sites in AAV genomes. Lastly, we demonstrate potential applications of USeqFISH for in situ AAV profiling and multimodal single-cell analysis in non-human primates." @default.
- W4318071669 created "2023-01-26" @default.
- W4318071669 creator A5010921137 @default.
- W4318071669 creator A5018653405 @default.
- W4318071669 creator A5029757025 @default.
- W4318071669 creator A5041227075 @default.
- W4318071669 creator A5050240445 @default.
- W4318071669 creator A5052164643 @default.
- W4318071669 creator A5054743790 @default.
- W4318071669 creator A5079998440 @default.
- W4318071669 date "2023-01-26" @default.
- W4318071669 modified "2023-10-14" @default.
- W4318071669 title "Spatial transcriptomics for profiling the tropism of viral vectors in tissues" @default.
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