Abstract
Background
Viral vectors have gained widespread use as vehicles for somatic gene transfer, and the targeted expression of foreign proteins by these vectors offers advantages over the systemic administration of the drugs in some therapeutic situations. Selective virus-mediated gene transfer to the peripheral nervous system (PNS), however, remains to be established. There are no data showing efficiency of protein transduction in the PNS, which consists of a variety of cell types, many of which are postmitotic.
Methods
We prepared the first-generation replication-deficient recombinant adenovirus vectors engineered to express LacZ. Eight-week-old Wister rats were used in this study. Adenovirus vector (5 µl) containing the LacZ gene (5 × 108 pfu) was injected into rat sciatic nerves or the dorsal root ganglia at the level of L5. The sciatic nerves, the dorsal root ganglia, and the spinal cords were obtained 7, 14, 21, and 28 days after injection. Expression of LacZ was assessed by X-gal histochemistry and β-gal immunohistochemistry.
Results
Following injection of the adenovirus carrying the LacZ gene into the sciatic nerve, LacZ expression was seen mainly in the Schwann cells and the small neurons in the dorsal root ganglion. In contrast, expression was observed in the primary nerve terminals of the spinal dorsal horn and the small to large dorsal root ganglion neurons and the Schwann cells after injection of the vectors into the L5 dorsal root ganglion. There were no side effects in rats with injection in the dorsal root ganglia or the sciatic nerve.
Conclusions
The present study shows efficient protein transduction by adenovirus vectors in the PNS. It is noted that injection of the virus into the dorsal root ganglia leads to extensive expression of LacZ in the spinal cord, the dorsal root ganglia, and the sciatic nerves.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
M Glatzel E Flechsig B Navarro MA Klein JC Paterna H Bueler et al. (2000) ArticleTitleAdenoviral and adeno-associated viral transfer of genes to the peripheral nervous system Proc Natl Acad Sci USA 97 442–7 10.1073/pnas.97.1.442 Occurrence Handle10.1073/pnas.97.1.442 Occurrence Handle1:CAS:528:DC%2BD3cXjvVGgtA%3D%3D Occurrence Handle10618437
TJMC Hermens RJ Giger AGD Holtmaat PA Dijkhuizen DA Houweling J Verhaagen (1997) ArticleTitleTransient gene transfer to neurons and glia: analysis of adenoviral vector performance in the CNS and PNS J Neurosci Methods 71 85–98 10.1016/S0165-0270(96)00129-X Occurrence Handle10.1016/S0165-0270(96)00129-X Occurrence Handle1:CAS:528:DyaK2sXhsFKrsLo%3D Occurrence Handle9125378
MG Kaplitt H Makimura (1997) ArticleTitleDefective viral vectors as agents for gene transfer in the nervous system J Neurosci Methods 71 125–32 10.1016/S0165-0270(96)00132-X Occurrence Handle10.1016/S0165-0270(96)00132-X Occurrence Handle1:CAS:528:DyaK2sXhsFKrs7s%3D Occurrence Handle9125381
M Phol J Braz (2001) ArticleTitleGene therapy of pain: emerging strategies and future directions Eur J Pharmacol 429 39–48 Occurrence Handle10.1016/S0014-2999(01)01304-8
M Yamada A Natsume M Mata T Oligino J Goss J Glorioso et al. (2001) ArticleTitleHerpes simplex virus vector-mediated expression of Bcl-2 protects spinal motor neurons from degeneration following root avulsion Exp Neurol 168 225–30 10.1006/exnr.2000.7597 Occurrence Handle10.1006/exnr.2000.7597 Occurrence Handle1:CAS:528:DC%2BD3MXhvFKjsL4%3D Occurrence Handle11259110
JR Goss M Mata WF Goins HH Wu JC Glorioso DJ Fink (2001) ArticleTitleAntinococeptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion Gene Ther 8 551–6 10.1038/sj.gt.3301430 Occurrence Handle10.1038/sj.gt.3301430 Occurrence Handle1:CAS:528:DC%2BD3MXis1emurk%3D Occurrence Handle11319622
CE Lilley F Groutsi Z Han JA Palmer PN Anderson DS Latchman et al. (2001) ArticleTitleMultiple immediate-early gene-deficient herpes simplex virus vectors allowing efficient gene delivery to neurons in culture and widespread gene delivery to the central nervous system in vivo J Virol 75 4343–56 Occurrence Handle10.1128/JVI.75.9.4343-4356.2001 Occurrence Handle1:CAS:528:DC%2BD3MXivFOktLc%3D Occurrence Handle11287583
M Chattopadhyay D Wolfe S Huang J Goss JC Glorioso M Mata et al. (2002) ArticleTitleIn vivo gene therapy for pyridoxine-induced neuropathy by herpes simplex virus-mediated gene transfer of neurotrophin-3 Ann Neurol 51 19–27 10.1002/ana.10061 Occurrence Handle10.1002/ana.10061 Occurrence Handle1:CAS:528:DC%2BD38XmvVOhsQ%3D%3D Occurrence Handle11782980
JA Palmer RH Branston CE Lilley MJ Robinson F Groutsi J Smith et al. (2000) ArticleTitleDevelopment and optimization of herpes simplex virus vectors for multiple long-term gene delivery to the peripheral nervous system J Virol 74 5604–28 10.1128/JVI.74.12.5604-5618.2000 Occurrence Handle10.1128/JVI.74.12.5604-5618.2000 Occurrence Handle1:CAS:528:DC%2BD3cXjvFansbw%3D Occurrence Handle10823868
SP Wilson DC Yeomans MA Bender Y Lu WF Goins JC Glorioso (1999) ArticleTitleAntihypalgesic effects of infection with a preproenkephalin-encoding herpes virus Proc Natl Acad Sci USA 96 3211–6 Occurrence Handle10.1073/pnas.96.6.3211 Occurrence Handle1:CAS:528:DyaK1MXhvFyktb4%3D Occurrence Handle10077663
S Miyake M Makimura Y Kanegae S Harada Y Sato K Takamori et al. (1996) ArticleTitleEfficient generation of recombinant adenoviruses using adenovirus DNA-terminal protein complex and a cosmid bearing the full-length virus genome Proc Natl Acad Sci USA 93 1320–4 10.1073/pnas.93.3.1320 Occurrence Handle10.1073/pnas.93.3.1320 Occurrence Handle1:CAS:528:DyaK28Xptl2quw%3D%3D Occurrence Handle8577762
Y Kanegae M Makimura I Saito (1994) ArticleTitleA simple and efficient method for purification of infectious recombinant adenovirus Jpn J Med Sci Biol 47 157–66 Occurrence Handle1:STN:280:DyaK2M7itlOntw%3D%3D Occurrence Handle7823411
Y Liu BT Himes J Moul W Huang SY Chow A Tessler et al. (1997) ArticleTitleApplication of recombinant adenovirus for in vivo gene delivery to spinal cord Brain Res 768 19–29 10.1016/S0006-8993(97)00587-8 Occurrence Handle10.1016/S0006-8993(97)00587-8 Occurrence Handle1:CAS:528:DyaK2sXlsleltrc%3D Occurrence Handle9369296
K Benihoud I Saggio P Opolon B Salone F Amiot E Connault et al. (1998) ArticleTitleEfficient, repeated adenovirous-mediated gene transfer in mice lacking both tumor necrosis factor alpha and lymphotoxin a J Virol 72 9514–25 Occurrence Handle1:CAS:528:DyaK1cXnsF2hurc%3D Occurrence Handle9811684
K Kajiwara AP Byrnes HM Charlton MJA Wood KJ Wood (1997) ArticleTitleImmune responses to adenoviral vectors during gene transfer in the brain Hum Gene Ther 8 253–65 Occurrence Handle10.1089/hum.1997.8.3-253 Occurrence Handle1:CAS:528:DyaK2sXhs1Khtrg%3D Occurrence Handle9048192
Author information
Authors and Affiliations
About this article
Cite this article
Watanabe, T., Ohtori, S., Koda, M. et al. Adenoviral gene transfer in the peripheral nervous system. J Orthop Sci 11, 64–69 (2006). https://doi.org/10.1007/s00776-005-0971-z
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s00776-005-0971-z