Efficiencies of transgene expression in nociceptive neurons through different routes of delivery of adeno-associated viral vectors

Ya Xu, Yanping Gu, Ping Wu, Guang Wen Li, Li-Yen Huang

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Transferring therapeutic genes into the nociceptive system, including dorsal root ganglia (DRGs) and the spinal cord, is potentially a powerful approach for the treatment of chronic pain in humans. Adeno-associated viral vectors (AAVs) are particularly useful in delivering foreign genes to targeted tissues because they seldom induce immune responses or produce cytotoxicity. To determine the efficiency of transgene expression and the best route(s) of delivery, a recombinant AAV type 2 vector containing the enhanced green fluorescent protein (EGFP) gene driven by the neuron-specific enolase (NSE) promoter (rAAV-EGFP) was constructed. We injected the vector into subcutaneous tissue, sciatic nerve, DRGs, and subarachnoid space, and examined EGFP expression in the DRG, spinal cord, and nerve fibers. Both sciatic nerve and DRG injection led to strong EGFP expression in a large number of DRG neurons. The expression persisted for more than 6-8 months. We then delivered the μ-opioid receptor (μOR) gene into DRGs through direct DRG or sciatic nerve injection of rAAV-υOR and found a significant increase in morphine efficacy. These results suggest that delivering therapeutic genes to DRGs by the rAAV-NSE vector is a valid strategy for treatment of chronic pain.

Original languageEnglish (US)
Pages (from-to)897-906
Number of pages10
JournalHuman Gene Therapy
Volume14
Issue number9
DOIs
StatePublished - Jun 10 2003

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Nociceptors
Spinal Ganglia
Transgenes
Sciatic Nerve
Phosphopyruvate Hydratase
Genes
Opioid Receptors
Chronic Pain
Spinal Cord
Spinal Nerves
Subarachnoid Space
Injections
Subcutaneous Tissue
Therapeutics
Nerve Fibers
Morphine
Neurons
enhanced green fluorescent protein

ASJC Scopus subject areas

  • Genetics

Cite this

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title = "Efficiencies of transgene expression in nociceptive neurons through different routes of delivery of adeno-associated viral vectors",
abstract = "Transferring therapeutic genes into the nociceptive system, including dorsal root ganglia (DRGs) and the spinal cord, is potentially a powerful approach for the treatment of chronic pain in humans. Adeno-associated viral vectors (AAVs) are particularly useful in delivering foreign genes to targeted tissues because they seldom induce immune responses or produce cytotoxicity. To determine the efficiency of transgene expression and the best route(s) of delivery, a recombinant AAV type 2 vector containing the enhanced green fluorescent protein (EGFP) gene driven by the neuron-specific enolase (NSE) promoter (rAAV-EGFP) was constructed. We injected the vector into subcutaneous tissue, sciatic nerve, DRGs, and subarachnoid space, and examined EGFP expression in the DRG, spinal cord, and nerve fibers. Both sciatic nerve and DRG injection led to strong EGFP expression in a large number of DRG neurons. The expression persisted for more than 6-8 months. We then delivered the μ-opioid receptor (μOR) gene into DRGs through direct DRG or sciatic nerve injection of rAAV-υOR and found a significant increase in morphine efficacy. These results suggest that delivering therapeutic genes to DRGs by the rAAV-NSE vector is a valid strategy for treatment of chronic pain.",
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AU - Li, Guang Wen

AU - Huang, Li-Yen

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