Serotype	Type	Transduction Efficiency	Best Use Case	Notes
AAV1	Natural	+++	Widespread local transduction	Excellent for cortical layers; often used for anterograde tracing.
AAV2	Natural	+++	Small, targeted brain nuclei	Limited diffusion; stays localized to the injection site. The “original” neuro-vector.
AAV5	Natural	+++	Deep brain structures	High efficiency in the substantia nigra and striatum. Transduces glia as well.
AAV9	Natural	+++++	Systemic CNS delivery	The gold standard for crossing the Blood-Brain Barrier (BBB) via IV injection.
AAVrh10	Natural	++++	Global brain targeting	Similar to AAV9 but sometimes shows higher efficiency in specific regions like the medulla.
AAV-DJ	Synthetic	+++++	In vitro & In vivo	A hybrid of 8 serotypes; extremely potent but highly immunogenic.
AAVrg (Retro)	Synthetic	+++++	Retrograde Tracing	Specifically engineered to travel from the axon tip back to the neuron’s cell body.
PHP.eB	Synthetic	++++++	Non-invasive whole-brain	An engineered AAV9 variant that is ~40x more efficient at crossing the BBB in mice.

Key Factors for Neuronal Targeting

While the Capsid (serotype) determines if the virus can enter the neuron, the Promoter inside the virus determines if the gene actually turns on. For true neuron-specific expression, scientists often combine the serotypes above with specific promoters:

• hSyn (Human Synapsin 1): The most common promoter used to restrict expression strictly to neurons (preventing expression in astrocytes or microglia).
• CaMKIIα: Used to target excitatory (glutamatergic) neurons, specifically in the forebrain/hippocampus.
• VGAT: Used to target inhibitory (GABAergic) neurons.

Summary of Delivery Routes

1. Intraparenchymal (Direct Injection): Use AAV1, AAV2, or AAV5. This is best if you only want to affect one specific “spot” in the brain.
2. Intrathecal (Spinal Tap): Use AAV9 or AAVrh10. This distributes the virus through the cerebrospinal fluid (CSF).
3. Intravenous (Systemic): Use AAV9 or PHP.eB. This allows you to target the entire brain without surgery, though it requires much higher doses.