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dc.contributor.authorBarati, Shahram
dc.contributor.authorHurtado, Plinio R.
dc.contributor.authorZhang, Shu H.
dc.contributor.authorTinsley, Rogan
dc.contributor.authorFerguson, Ian A.
dc.contributor.authorRush, Robert A.
dc.date.accessioned2017-05-03T16:57:55Z
dc.date.available2017-05-03T16:57:55Z
dc.date.issued2006
dc.date.modified2010-01-07T02:17:10Z
dc.identifier.issn00144886
dc.identifier.doi10.1016/j.expneurol.2006.05.027
dc.identifier.urihttp://hdl.handle.net/10072/28087
dc.description.abstractThe retrograde axonal transport mechanism of motor neurons has been exploited to deliver the gene encoding Glial cell line-derived neurotrophic factor (GDNF) into the central nervous system to provide trophic support following injury. A nonviral gene delivery system, consisting of a monoclonal antibody (MC192) that binds the neurotrophic receptor, p75NTR, coupled to poly-L-lysine, was constructed and used to deliver the gene via a receptor-mediated mechanism. The MC192-poly-l-lysine/pGDNF complex was injected into the hind limb of newborn rats to allow gene expression within motor neurons prior to sciatic nerve transection. In adult rats, the gene delivery complex was administrated in gel foam placed on a transected hypoglossal nerve. We show that the delivered construct is internalized following binding to p75NTR and is transported into the brain and spinal cord, bypassing the blood-brain barrier. The presence of the GDNF transgene and its transcript could be detected for up to 8 weeks in spinal cord and brain stem. Expression of the GDNF protein rescued 38% of the targeted motor neurons 1 week postinjury in newborn rats while the survival rate in control group was below 12%. In adult rats, neuronal death induced by axotomy was almost completely reversed by the introduction of the transgene (95 ᠳ%). Thus, the significant functional outcomes of this novel gene delivery system are demonstrated both in postnatal and adult motor neurons.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom179
dc.relation.ispartofpageto188
dc.relation.ispartofissue1
dc.relation.ispartofjournalExperimental Neurology
dc.relation.ispartofvolume202
dc.rights.retentionY
dc.subject.fieldofresearchGene and Molecular Therapy
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchNeurosciences
dc.subject.fieldofresearchPsychology
dc.subject.fieldofresearchcode100401
dc.subject.fieldofresearchcode1103
dc.subject.fieldofresearchcode1109
dc.subject.fieldofresearchcode1701
dc.titleGDNF gene delivery via the p75NTR receptor rescues injured motor neurons
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2006
gro.hasfulltextNo Full Text
gro.griffith.authorFerguson, Ian


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