This is organized by Natural Serotypes (found in nature) and Engineered Capsids (specifically designed to overcome ocular barriers).

Quick Legend: Administration Routes

• SR (Subretinal): Injected between the retina and RPE. Bypasses the Inner Limiting Membrane (ILM). Best for outer retina (Photoreceptors/RPE).
• IVT (Intravitreal): Injected into the vitreous humor. Less invasive, but the vector must penetrate the ILM to reach the retina.
• AC (Intracameral): Injected into the anterior chamber (front of the eye).

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1. Natural AAV Serotypes

Serotype	Primary Target Cells	Preferred Route	Key Characteristics & Notes
AAV2	RPE, Ganglion Cells (RGCs)	SR (for RPE) IVT (for RGCs)	The historical gold standard (Luxturna uses AAV2). • SR: Excellent RPE transduction. • IVT: Mostly restricted to RGCs; poor penetration to outer retina due to heparan sulfate binding at the ILM.
AAV5	Photoreceptors (Rods/Cones), RPE	SR	Faster and more efficient than AAV2 in photoreceptors. • Can package slightly larger genomes (~5kb). • Poor transduction via IVT.
AAV8	Photoreceptors, RPE	SR	High efficiency and rapid onset of expression. • Often considered superior to AAV2/5 for photoreceptors. • Can diffuse laterally better than AAV2 in the subretinal space (covering a wider area).
AAV9	RPE, Müller Glia, Photoreceptors (cones > rods)	SR / IVT	Broad tropism. • IVT: Can penetrate the ILM better than AAV2/5/8, reaching some Müller glia and photoreceptors, but still less efficient than engineered capsids. • Note: High risk of off-target expression in the liver if it escapes the eye.
AAV1	RPE, Corneal Epithelium	SR / AC	Less commonly used for retina now (superseded by AAV8), but has shown utility in corneal epithelium via intrastromal or AC injection.

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2. Engineered & Synthetic Capsids

These are designed specifically to cross barriers (like the ILM) or target difficult cells (like Müller Glia).

Variant	Primary Target Cells	Preferred Route	Key Characteristics & Notes
AAV2-7m8	Photoreceptors (Rods/Cones), RGCs	IVT	“The Deep Penetrator.” • Designed specifically to cross the Inner Limiting Membrane (ILM) following a simple intravitreal injection. • Allows pan-retinal transduction of photoreceptors without the surgical risk of subretinal injection.
ShH10	Müller Glia	IVT	Müller-Specific. • Engineered (from AAV6) specifically to target Müller glial cells via the vitreous. • Essential for therapies requiring glia-secreted neurotrophic factors.
AAV-DJ	RPE, Photoreceptors	SR	High Efficiency Hybrid. • A chimera of types 2, 8, and 9. • Higher infectivity rates in vitro and in vivo compared to wild types.
Anc80L65	RPE, Photoreceptors, Trabecular Meshwork, Cornea	SR / AC	Anterior Segment Potency. • A synthetic “ancestral” AAV. • Uniquely high efficiency in the anterior segment (Cornea/TM) via AC injection. • Highly potent in retina via SR.
AAV8b(t)	Photoreceptors	SR	Variant of AAV8 with lower immunogenicity or enhanced diffusion in some models.

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3. Tropism by Target Tissue

If you are targeting a specific cell type, start here:

• Retinal Pigment Epithelium (RPE): AAV2, AAV5, AAV8 (via Subretinal).
• Photoreceptors (Rods/Cones): AAV8 or AAV5 (Subretinal); AAV2-7m8 (Intravitreal).
• Retinal Ganglion Cells (RGCs): AAV2 (Intravitreal).
• Müller Glia: ShH10 (Intravitreal).
• Corneal Endothelium/Stromal: AAV8, Anc80L65 (Intracameral/Intrastromal).
• Trabecular Meshwork (Glaucoma): Anc80L65, scAAV2 (Intracameral).

Critical Factor: The Inner Limiting Membrane (ILM)

When selecting a serotype, the route dictates the success.

• Problem: The ILM is a physical barrier separating the vitreous from the retina. Natural serotypes (AAV2, 5, 8) cannot easily cross it.
• Solution:
  • If you use AAV8: You must inject Subretinally (surgery required) to bypass the ILM.
  • If you want to inject Intravitreally (office procedure): You likely need an engineered capsid like AAV2-7m8 to cross the ILM and reach the photoreceptors.