AAV Tropism for Spinal and DRG Tissues

Targeting the spine involves two distinct zones: the Spinal Cord (CNS) and the Dorsal Root Ganglia (DRG), which house the sensory neurons.

While AAV9 is the most famous for its use in Spinal Muscular Atrophy (SMA) therapy, other natural and engineered serotypes are often preferred depending on whether you are targeting motor neurons, sensory neurons, or glial cells.

Serotype	Primary Target	Transduction Efficiency	Best Route	Key Applications
AAV9	Motor Neurons	Very High	IV / Intrathecal	The gold standard for SMA (Zolgensma). Excellent at crossing the BBB and spreading throughout the spinal cord.
AAVrh10	Motor Neurons & Glia	High	IV / Intrathecal	Often shows higher expression than AAV9 in the dorsal spinal cord and lower motor neurons at lower doses.
AAV6	Sensory Neurons (DRG)	High	Direct DRG / Intrathecal	Preferred for targeting primary sensory neurons; excellent for chronic pain and nerve injury research.
AAV5	Astrocytes	Very High	Intraparenchymal	The most “gliophilic” natural serotype; used to target spinal astrocytes in neurodegenerative studies.
AAV1	Neurons & Muscle	Moderate/High	Intramuscular (Retrograde)	Can be taken up by nerve terminals in muscle and transported back to the spinal cord (retrograde).
AAV-PHP.eB	Pan-Spinal	Ultra High	Systemic (IV)	Engineered; roughly 40x more efficient than AAV9 at crossing the BBB to reach the spinal cord in rodents.
AAVrg	Projection Neurons	Ultra High	Local Injection	Engineered for retrograde transport; used to map which brain regions connect to specific spinal segments.

Delivery Strategies for the Spine

The “Spine” is a long, protected structure, so the injection site determines the reach:

• Intravenous (IV): Used for global coverage (e.g., SMA). Requires high doses. Only AAV9, AAVrh10, and PHP.eB are effective here.
• Intrathecal (IT): Injecting into the cerebrospinal fluid (CSF) via a lumbar puncture. This concentrates the virus around the spinal cord while using a much lower dose than IV. AAV9 and AAV6 are top choices.
• Intraparenchymal: Direct injection into the spinal cord tissue. This is the most invasive but provides highly localized expression. AAV5 is often used here for glial research.
• Direct DRG Injection: Targeting the “bulges” on the side of the spine. This is the most efficient way to target sensory neurons for pain research.

Selecting Spinal-Specific Promoters

To refine your targeting within the spinal cord, pair your serotype with these promoters:

• hSyn / mecp2: Restricts expression to Spinal Neurons.
• GFAP: Restricts expression to Astrocytes (useful for spinal cord injury/scarring research).
• Chat (Choline Acetyltransferase): A larger promoter used to specifically target Motor Neurons.
• Advillin: Highly specific for Sensory Neurons in the Dorsal Root Ganglia.

The “Retrograde” Advantage

If you want to treat the spinal cord but avoid a spinal injection, you can use Retrograde transport. By injecting AAVrg or AAV6 into a muscle, the virus can travel “backward” along the axon to reach the motor neurons sitting in the spinal cord.