Journal
GENE THERAPY
Volume 16, Issue 4, Pages 461-469Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2009.23
Keywords
pain; dorsal root ganglion; AAV; endorphin; IL-10
Categories
Funding
- National Institute of Neurological Disorders and Stroke [K08NS046012, 1R01NS063022]
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Recombinant adeno-associated virus (rAAV) vectors consisting of self-complementary genomes and packaged in certain capsids can target primary sensory neurons efficiently and can control neuropathic pain long term by expressing opioid or non-opioid analgesic genes. This review examines the therapeutic potential of the approach in five sections: Pain control in oncology (including a discussion of cancer centers as translational pain research environment); vector biology; safety considerations and immunological lessons learned from rAAV clinical trials of other disorders; development of intrathecal rAAV therapy in rodent models of pain; and preclinical steps towards clinical translation of rAAV for pain. In the field of analgesic drug development, clinical validation of new approaches identified in rodents is currently a critical limiting step. Small-molecule therapeutics suitable as conventional drugs to probe novel targets in clinical trials are often unavailable. In this context, gene therapy could fill an important gap in the drug development process facilitating first-into-human trials of untested targeted treatments, each instantiated as a therapeutic gene.
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