Efficient Retrograde Transport of AAV8 to Spinal Cord and Dorsal Root Ganglion a

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Hum Gene Ther. 2009 Aug 31.

Efficient Retrograde Transport of AAV8 to Spinal Cord and Dorsal Root Ganglion

after Vector Delivery in Muscle.

Zheng H, Qiao C, Wang CH, Li J, Li J, Yuan Z, Zhang C, Xiao X.

The First Affiliated Hospital of Sun Yet-sen University, Department of

Neurology, Guangzhou city, Guangdong Province, China

The peripheral nervous system (PNS), including peripheral nerves and dorsal root

ganglia (DRG), is involved in numerous neurological disorders, such as

peripheral neuropathies (diabetic neuropathy and chronic pain, etc) and

demyelination diseases (multiple sclerosis, congenital muscular dystrophy and

Charcot-Marie-Tooth disease, etc).

Effective clinical interventions for those diseases are very limited.

Gene therapy represents a novel therapeutic strategy for the PNS diseases,

especially with simply and minimally invasive delivery methods.

Previously, we showed that AAV8 can efficiently transduce muscles bodywide by a

simple intraperitoneal (i.p.) injection in neonatal mice. In this study, we

investigated the capacity of AAV8 in transducing PNS in neonatal mice by i.p.

injection and also in adult mice by intramuscular injection.

Efficient and long-term gene transfer was found in the white matter of the

spinal cord, DRG neurons and peripheral nerves in both groups, treated either as

neonates or as adults, particularly neonates. In the adult mice injected with

AAV8 in tibialis anterior (TA) and gastrocnemius (GAS) muscles in one of the

hindlegs, more neurons were transduced in the lower part of the spinal cord than

the upper part; the DRG neurons were transduced more on the vector-injected side

than in the contralateral uninjected side. Few cells in the grey matter of the

spinal cord were transduced regardless of the delivery methods and age of the

mice.

These results support the mechanism of vector retrograde transport and suggest

that AAV8 crosses blood-nerve barrier poorly.

Our finding should have important implications in gene therapy for peripheral

neurological disorders.