Field-leading intravenous gene delivery to the CNS
to of the in the CNS
Well-tolerated and easy to administer.
Able to reach enough cells for clinical efficacy.
Transduction data with cell-type resolution to ensure delivery to clinically relevant cell types.
The Dyno bCap 1 vector
The Dyno bCap 1 vector crosses the blood-brain barrier after IV injection, enabling safer and less-invasive delivery at a low dose to diverse cells throughout the CNS.
Dyno’s AI-powered design platform identified 7 sequence edits, to transform AAV9 into the bCap 1 capsid and improve delivery.
Dyno bCap 1 data
The Dyno bCap 1 capsid reaches 5-20% of neurons and clinically relevant neuronal populations across the CNS at a low dose of 1e13 vg/kg in NHPs
The Dyno bCap 1 capsid has minimal off-target effects on the liver and the DRG, reducing potential for adverse effects
Dyno bCap 1 produces with comparable efficiency to WT AAV9
Dyno bCap 1 has been validated extensively with consistent performance across multiple NHP species in repeated experiments, maximizing the potential for translatability to humans
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 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.
The Dyno bCap 1 capsid offers…
Precise delivery to enough of the right cells
Transduction of 5-20% of neurons in the CNS at a low IV dose of 1e13 vg/kg in NHPs, with the potential for higher transduction at higher doses.
Field-leading performance for CNS IV delivery
Greatest all-around potential for CNS delivery with:
100x brain transduction vs AAV9
10x liver detargeting vs AAV9
1x production vs AAV9
Superiority in head-to-head data comparisons
Dyno bCap 1 transduces more consistently and produces more efficiently than external engineered capsids tested side-by-side in the same experiments.