The Dyno bCap 1 capsid transduces 5-21% of neurons in the CNS. Quantified histology data from Cyno NHP dosed intravenously with equal ratios of Dyno bCap 1 capsid and AAV9 capsid in a single test article at a dose of 1E13 vg/kg and 6E12 vg/kg per variant in two replicates.

10% of cells transduced, 13% of Fox3+ neurons transduced in the motor cortex. Representative RNAscope images of Dyno bCap 1-eGFP (green) and AAV9-mCherry (magenta) reporters with DAPI staining (blue) in Cyno NHP at 1e13 vg/kg dose. Arrows denote rare AAV9+ cells.

Dyno bCap 1 efficiently transduces upper and lower motor neurons. Data obtained from RNAscope quantification of spinal cord and premotor cortex at high and low dose IV injection into Cyno NHP.

The Dyno bCap 1 capsid efficiently transduces dopaminergic neurons in the substantia nigra. Data obtained from RNAscope quantification of high and low dose IV injection into Cyno NHP.

Dyno bCap 1 efficiently transduces medium spiny neurons in striatum. Data obtained from RNAscope quantification of high and low dose IV injection into Cyno NHP.

Bulk NGS measurements show 10x liver detargeting for Dyno bCap 1 capsid vs AAV9. Rates of transduction and biodistribution relative to AAV9 as measured by NGS of expressed barcodes and viral genomes, respectively, extracted from bulk tissue and normalized to initial representation in test article.

Off-target DRG transduction for Dyno bCap 1 capsid is similar to AAV9. Representative RNAscope images of Dyno bCap 1-eGFP (green) and AAV9-mCherry (magenta) reporters with DAPI staining (blue) in Cyno NHP at 1e13 vg/kg dose.

The Dyno bCap 1 capsid is a good producer under standard conditions. Quantification of yields from replicate single-capsid productions of the Dyno bCap 1 capsid and an external engineered capsid done using standard triple transfection.

The Dyno bCap 1 capsid demonstrates highly consistent performance vs. other engineered capsids across animals and experiments. Rates of transduction relative to AAV9 as measured by NGS of expressed barcodes from bulk tissue, normalized to initial representation in test article. Each row shows an individual NHP replicate.

Increased Rate of Dyno bCap 1 Transduction is Consistent Between RNAscope and Bulk NGS. Median number of detected Dyno bCap 1 capsid expressed barcodes per μg tissue RNA (x axis) and mean percentage of positive cells in RNAscope histology (y axis) show a Pearson correlation of 0.93.