BACKGROUND: Direct injection of lentivectors into the central nervous system (CNS) mostly results in localized parenchymal transgene expression. Intrathecal gene delivery into the spinal canal may produce a wider dissemination of the transgene and allow diffusion of secreted transgenic proteins throughout the cerebrospinal fluid (CSF). Herein, we analyze the distribution and expression of LacZ and SEAP transgenes following the intrathecal delivery of lentivectors into the spinal canal. METHODS: Four weeks after intrathecal injection into the spinal canal of newborn mice, the expression of the LacZ gene was assessed by histochemical staining and by in situ polymer chain reaction (PCR). Following the spinal infusion of a lentivector carrying the SEAP gene, levels of enzymatically active SEAP were measured in the CSF, blood serum, and in brain extracts. RESULTS: Intrathecal spinal canal delivery of lentivectors to newborn mice resulted in patchy, widely scattered areas of beta-gal expression mostly in the meninges. The transduction of the meningeal cells was confirmed by in situ PCR. Following the spinal infusion of a lentivector carrying the SEAP gene, sustained presence of the reporter protein was detected in the CSF, as well as in blood serum, and brain extracts. CONCLUSIONS: These findings indicate that intrathecal injections of lentivectors can provide significant levels of transgene expression in the meninges. Unlike intracerebral injections of lentivectors, intrathecal gene delivery through the spinal canal appears to produce a wider diffusion of the transgene. This approach is less invasive and may be useful to address those neurological diseases that benefit from the ectopic expression of soluble factors impermeable to the blood-brain barrier. Copyright 2006 John Wiley & Sons, Ltd.
BACKGROUND: Direct injection of lentivectors into the central nervous system (CNS) mostly results in localized parenchymal transgene expression. Intrathecal gene delivery into the spinal canal may produce a wider dissemination of the transgene and allow diffusion of secreted transgenic proteins throughout the cerebrospinal fluid (CSF). Herein, we analyze the distribution and expression of LacZ and SEAP transgenes following the intrathecal delivery of lentivectors into the spinal canal. METHODS: Four weeks after intrathecal injection into the spinal canal of newborn mice, the expression of the LacZ gene was assessed by histochemical staining and by in situ polymer chain reaction (PCR). Following the spinal infusion of a lentivector carrying the SEAP gene, levels of enzymatically active SEAP were measured in the CSF, blood serum, and in brain extracts. RESULTS: Intrathecal spinal canal delivery of lentivectors to newborn mice resulted in patchy, widely scattered areas of beta-gal expression mostly in the meninges. The transduction of the meningeal cells was confirmed by in situ PCR. Following the spinal infusion of a lentivector carrying the SEAP gene, sustained presence of the reporter protein was detected in the CSF, as well as in blood serum, and brain extracts. CONCLUSIONS: These findings indicate that intrathecal injections of lentivectors can provide significant levels of transgene expression in the meninges. Unlike intracerebral injections of lentivectors, intrathecal gene delivery through the spinal canal appears to produce a wider diffusion of the transgene. This approach is less invasive and may be useful to address those neurological diseases that benefit from the ectopic expression of soluble factors impermeable to the blood-brain barrier. Copyright 2006 John Wiley & Sons, Ltd.
Authors: Kathryn S Linterman; David N Palmer; Graham W Kay; Lucy A Barry; Nadia L Mitchell; Robin G McFarlane; Michael A Black; Mark S Sands; Stephanie M Hughes Journal: Hum Gene Ther Date: 2011-05-19 Impact factor: 5.695
Authors: Lorenzo Battini; Salvador Macip; Elena Fedorova; Steven Dikman; Stefan Somlo; Cristina Montagna; G Luca Gusella Journal: Hum Mol Genet Date: 2008-06-19 Impact factor: 6.150
Authors: Travis S Hughes; Stephen J Langer; Kirk W Johnson; Raymond A Chavez; Linda R Watkins; Erin D Milligan; Leslie A Leinwand Journal: Mol Ther Date: 2008-10-21 Impact factor: 11.454
Authors: Alexia Kagiava; Irene Sargiannidou; George Theophilidis; Christos Karaiskos; Jan Richter; Stavros Bashiardes; Natasa Schiza; Marianna Nearchou; Christina Christodoulou; Steven S Scherer; Kleopas A Kleopa Journal: Proc Natl Acad Sci U S A Date: 2016-03-28 Impact factor: 11.205
Authors: Raphael Rozenfeld; Ittai Bushlin; Ivone Gomes; Nikos Tzavaras; Achla Gupta; Susana Neves; Lorenzo Battini; G Luca Gusella; Alexander Lachmann; Avi Ma'ayan; Robert D Blitzer; Lakshmi A Devi Journal: PLoS One Date: 2012-01-03 Impact factor: 3.240