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A bicistronic lentiviral vector encoding both the hexosaminidase \u03b1 and \u03b2 chains (SIV.ASB) has previously been shown to correct the \u03b2\u2010hexosaminidase deficiency and to reduce GM2 levels both in transduced and cross\u2010corrected human Sandhoff fibroblasts. Recent advances in determining the neuropathophysiological mechanisms in Sandhoff disease have shown a mechanistic link between GM2 accumulation, neuronal cell death, reduction of sarcoplasmic\/endoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>\u2010ATPase (SERCA) activity, and axonal outgrowth. To examine the ability of the SIV.ASB vector to reverse these pathophysiological events, hippocampal neurons from embryonic Sandhoff mice were transduced with the lentivector. Normal axonal growth rates were restored, as was the rate of Ca<jats:sup>2+<\/jats:sup> uptake via the SERCA and the sensitivity of the neurons to thapsigargin\u2010induced cell death, concomitant with a decrease in GM2 and GA2 levels. Thus, we have demonstrated that the bicistronic vector can reverse the biochemical defects and down\u2010stream consequences in Sandhoff neurons, reinforcing its potential for Sandhoff disease <jats:italic>in vivo<\/jats:italic> gene therapy.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2006.03665.x","type":"journal-article","created":{"date-parts":[[2006,1,25]],"date-time":"2006-01-25T12:15:38Z","timestamp":1138191338000},"page":"1572-1579","source":"Crossref","is-referenced-by-count":8,"title":["Reversion of the biochemical defects in murine embryonic Sandhoff neurons using a bicistronic lentiviral vector encoding hexosaminidase \u03b1 and \u03b2"],"prefix":"10.1111","volume":"96","author":[{"given":"Audrey","family":"Arfi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivka","family":"Zisling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Richard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Batista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Poenaru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony H.","family":"Futerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Caillaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,1,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.04.017"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-3862(99)00021-2"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199105233242104"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-19-08199.1999"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490350513"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.7.8.2745"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64849-5"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1423"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2004.03.003"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-122-1-199501010-00005"},{"key":"e_1_2_7_12_1","first-page":"3827","volume-title":"The Metabolic and Molecular Basis of Inherited disease","author":"Gravel R. 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