Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1930
Glatzel, M; Flechsig, E; Navarro, B; Klein, M A; Paterna, J C; Büeler, H; Aguzzi, A (2000). Adenoviral and adeno-associated viral transfer of genes to the peripheral nervous system. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 97(1):442-447.
Targeted expression of foreign genes to the peripheral nervous system is interesting for many applications, including gene therapy of neuromuscular diseases, neuroanatomical studies, and elucidation of mechanisms of axonal flow. Here we describe a microneurosurgical technique for injection of replication-defective viral vectors into dorsal root ganglia (DRG). Adenovirus- and adeno-associated virus-based vectors with transcriptional competence for DRG neurons led to expression of the gene of interest throughout the first neuron of the sensory system, from the distal portions of the respective sensory nerve to the ipsilateral nucleus gracilis and cuneatus, which contains the synapses to the spinothalamic tracts. Use of Rag-1 ablated mice, which lack all B and T lymphocytes, allowed for sustained expression for periods exceeding 100 days. In immunocompetent mice, long-term (52 days) expression was achieved with similar efficiency by using adeno-associated viral vectors. DRG injection was vastly superior to intraneural injection into the sciatic nerve, which mainly transduced Schwann cells in the vicinity of the site of inoculation site but only inefficiently transduced nerve fibers, whereas i.m. injection did not lead to any significant expression of the reporter gene in nerve fibers. The versatile and efficient transduction of genes of interest should enable a wide variety of functional studies of peripheral nervous system pathophysiology.
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|Item Type:||Journal Article, refereed|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology|
|Dewey Decimal Classification:||570 Life sciences; biology
610 Medicine & health
|Date:||4 January 2000|
|Deposited On:||11 Feb 2008 12:26|
|Last Modified:||23 Nov 2012 13:22|
|Publisher:||National Academy of Sciences|
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