Adeno-associated virus (AAV) vectors are a leading delivery platform for central nervous system (CNS) gene therapy because they combine relatively low pathogenicity, durable transgene expression, and adaptable tissue tropism.[1][2] In neurodegeneration, those properties matter because effective therapy usually depends on getting a therapeutic payload into neurons and glia across the blood-brain barrier or through direct cerebrospinal fluid delivery.[1:1][3]
Adeno-associated virus (AAV) vectors are widely used for CNS gene transfer because they can support long-term expression, can be engineered for cell-type selectivity, and in the case of serotypes such as AAV9 can achieve clinically relevant CNS delivery after systemic administration.[1:2][3:1]
| Serotype | BBB Crossing | Neuronal Tropism | Key Use |
|---|---|---|---|
| AAV9 | Yes (high) | Excellent | Systemic delivery |
| AAVrh.10 | Yes | Excellent | Broad CNS targeting |
| PHP.B / PHP.eB | Yes (mouse-biased) | Excellent | Research / preclinical engineering |
| AAV2 | Limited | Good | Direct injection |
| AAV5 | Limited | Good | Striatal delivery and HD programs |
| AAV1 | Limited | Good | Peripheral and spinal applications |
| Product | Indication | Year |
|---|---|---|
| Luxturna | Leber congenital amaurosis | 2017 |
| Zolgensma | Spinal muscular atrophy | 2019 |
| Ryplazim | Plasminogen deficiency | 2023 |
No AAV therapy is yet FDA approved specifically for a CNS neurodegenerative disease, but the platform has already demonstrated regulatory viability in closely related neurologic indications.[4:1]
The rapid rise of AAV-based therapeutics reflects converging improvements in capsid engineering, promoter design, neurosurgical delivery, and large-scale vector manufacturing. Those advances have turned CNS gene therapy from a purely experimental strategy into a realistic therapeutic platform for neurodegenerative disease programs.[1:9][4:2]
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