{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:02:27Z","timestamp":1779336147759,"version":"3.51.4"},"reference-count":42,"publisher":"Portland Press Ltd.","issue":"6","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:p>The cellular and molecular environment present in the fetus and early newborn provides an excellent opportunity for effective gene transfer. Innate and pre-existing anti-vector immunity may be attenuated or absent and the adaptive immune system predisposed to tolerance towards xenoproteins. Stem cell and progenitor cell populations are abundant, active and accessible. In addition, for treatment of early lethal genetic diseases of the nervous system, the overarching advantage may be that early gene supplementation prevents the onset of irreversible pathological changes. Gene transfer to the fetal mouse nervous system was achieved, albeit inefficiently, as far back as the mid-1980s. Recently, improvements in vector design and production have culminated in near-complete correction of a mouse model of spinal muscular atrophy. In the present article, we review perinatal gene transfer from both a therapeutic and technological perspective.<\/jats:p>","DOI":"10.1042\/bst0381489","type":"journal-article","created":{"date-parts":[[2010,12,1]],"date-time":"2010-12-01T15:07:34Z","timestamp":1291216054000},"page":"1489-1493","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<i>In utero<\/i> gene transfer to the mouse nervous system"],"prefix":"10.1042","volume":"38","author":[{"given":"Ahad\u00a0A.","family":"Rahim","sequence":"first","affiliation":[{"name":"Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew\u00a0M.S.","family":"Wong","sequence":"additional","affiliation":[{"name":"Paediatric Storage Disease Laboratory, Institute of Psychiatry, Kings College London, 125 Coldharbour Lane, London SE5 9NU, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne\u00a0M.K.","family":"Buckley","sequence":"additional","affiliation":[{"name":"Department of Haematology, University College Medical School, Rowland Hill Street, London NW3 2PF, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerry\u00a0K.Y.","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Maternal and Fetal Medicine, Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna\u00a0L.","family":"David","sequence":"additional","affiliation":[{"name":"Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan\u00a0D.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Paediatric Storage Disease Laboratory, Institute of Psychiatry, Kings College London, 125 Coldharbour Lane, London SE5 9NU, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Coutelle","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, South Kensington, London SW7 2AZ, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald\u00a0M.","family":"Peebles","sequence":"additional","affiliation":[{"name":"Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon\u00a0N.","family":"Waddington","sequence":"additional","affiliation":[{"name":"Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2010,11,24]]},"reference":[{"key":"2021111909571505200_B1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1001\/jama.281.3.249","article-title":"Prevalence of lysosomal storage disorders","volume":"281","author":"Meikle","year":"1999","journal-title":"JAMA, J. 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U.S.A."},{"key":"2021111909571505200_B13","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/sj.gt.3301700","article-title":"Adenovirus-mediated prenatal gene transfer to murine central nervous system","volume":"9","author":"Shen","year":"2002","journal-title":"Gene Ther."},{"key":"2021111909571505200_B14","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1002\/jgm.630","article-title":"Widespread gene transduction to the central nervous system by adenovirus in utero: implication for prenatal gene therapy to brain involvement of lysosomal storage disease","volume":"6","author":"Shen","year":"2004","journal-title":"J. Gene Med."},{"key":"2021111909571505200_B15","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.ymthe.2005.11.011","article-title":"Neuronal precursor-restricted transduction via in utero CNS gene delivery of a novel bipartite HSV amplicon\/transposase hybrid vector","volume":"13","author":"Bowers","year":"2006","journal-title":"Mol. 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Gynecol."},{"key":"2021111909571505200_B28","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1126\/science.1734520","article-title":"Widespread dispersion of neuronal clones across functional regions of the cerebral cortex","volume":"255","author":"Walsh","year":"1992","journal-title":"Science"},{"key":"2021111909571505200_B29","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1242\/dev.104.3.473","article-title":"Cell lineage in the rat cerebral cortex: a study using retroviral-mediated gene transfer","volume":"104","author":"Price","year":"1988","journal-title":"Development"},{"key":"2021111909571505200_B30","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/0896-6273(88)90163-8","article-title":"Cell lineage in the cerebral cortex of the mouse studied in vivo and in vitro with a recombinant retrovirus","volume":"1","author":"Luskin","year":"1988","journal-title":"Neuron"},{"key":"2021111909571505200_B31","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/sj.mt.6300092","article-title":"Gene transfer to ocular stem cells by early gestational intraamniotic injection of lentiviral vector","volume":"15","author":"Endo","year":"2007","journal-title":"Mol. 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Neurol."},{"key":"2021111909571505200_B34","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/cne.21945","article-title":"Development of the mouse amygdala as revealed by enhanced green fluorescent protein gene transfer by means of in utero electroporation","volume":"513","author":"Soma","year":"2009","journal-title":"J. Comp. Neurol."},{"key":"2021111909571505200_B35","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1242\/dev.02283","article-title":"Direct visualization of nucleogenesis by precerebellar neurons: involvement of ventricle-directed, radial fibre-associated migration","volume":"133","author":"Kawauchi","year":"2006","journal-title":"Development"},{"key":"2021111909571505200_B36","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/1471-213X-7-103","article-title":"Gene delivery into mouse retinal ganglion cells by in utero electroporation","volume":"7","author":"Garcia-Frigola","year":"2007","journal-title":"BMC Dev. Biol."},{"key":"2021111909571505200_B37","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.neuron.2010.01.019","article-title":"Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits","volume":"65","author":"Niwa","year":"2010","journal-title":"Neuron"},{"key":"2021111909571505200_B38","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nature07265","article-title":"Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer","volume":"455","author":"Gubbels","year":"2008","journal-title":"Nature"},{"key":"2021111909571505200_B39","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1172\/JCI41615","article-title":"CNS-targeted gene therapy improves survival and motor function in a mouse model of spinal muscular atrophy","volume":"120","author":"Passini","year":"2010","journal-title":"J. Clin. 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