A Single Injection of Recombinant Adeno-Associated Virus into the Lumbar Cistern Delivers Transgene Expression Throughout the Whole Spinal Cord
UMass Chan Affiliations
Viral Vector CoreDepartment of Microbiology and Physiology Systems
Gene Therapy Center
Department of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2015-07-01Keywords
AAVAmyotrophic lateral sclerosis
Gene therapy
Pain
SMA
rAAV
Molecular and Cellular Neuroscience
Nervous System Diseases
Therapeutics
Metadata
Show full item recordAbstract
The lack of methods to deliver transgene expression in spinal cord has hampered investigation of gene function and therapeutic targets for spinal cord diseases. Here, we report that a single intrathecal injection of recombinant adeno-associated virus rhesus-10 (rAAVrh10) into the lumbar cistern led to transgene expression in 60 to 90 % of the cells in the spinal cord. The transgene was expressed in all cell types, including neurons, glia, ependymal cells, and endothelial cells. Additionally, the transgene was expressed in some brain areas up to the frontal cortex and the olfactory bulb. The rAAV was distributed predominantly in the spinal cord, where its genome copy was over ten times that of the peripheral organs. Compared with intravenous injection, another method for rAAV delivery to the broad central nervous system (CNS), the intrathecal injection reduced the dosage of rAAV required to achieve similar or higher levels of transgene expression in the CNS by ~100-fold. Finally, the transduced areas were co-localized with the perivascular spaces of Virchow-Robin, from which the rAAV spreads further into the CNS parenchyma, thus suggesting that rAAV penetrated the CNS parenchyma through this pathway. Taken together, we have defined a fast and efficient method to deliver widespread transgene expression in mature spinal cord in mice. This method can be applied to stably overexpress or silence gene expression in the spinal cord to investigate gene functions in mammalian CNS. Additionally, this method can be applied to validate therapeutic targets for spinal cord diseases.Source
Mol Neurobiol. 2016 Jul;53(5):3235-48. doi: 10.1007/s12035-015-9223-1. Epub 2015 Jun 7. Link to article on publisher's siteDOI
10.1007/s12035-015-9223-1Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39993PubMed ID
26050084Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1007/s12035-015-9223-1