{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:04:51Z","timestamp":1791198291845,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,1,31]],"date-time":"2005-01-31T00:00:00Z","timestamp":1107129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Brain\u2010directed prenatal gene therapy may benefit some lysosomal storage diseases that affect the central nervous system (CNS) before birth. Our previous study showed that intrauterine introduction of recombinant adenoviruses into cerebral ventricles results in efficient gene transfer to the CNS in the mouse. However, transgene expression decreased with time due to the non\u2010integrative property of adenoviral vectors. In this study, in order to obtain permanent gene transduction, we investigated the feasibility of retrovirus\u2010mediated <jats:italic>in utero<\/jats:italic> gene transduction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Concentrated retrovirus encoding the LacZ gene was injected into the cerebral ventricles of the embryos of normal and twitcher mice (a murine model of Krabbe disease) at embryonic day 12. The distribution and maintenance of the transgene expression in the recipient brain were analyzed histochemically, biochemically and by the quantitative polymerase chain reaction method pre\u2010 and postnatally.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Efficient and highly persistent gene transduction to the brain was achieved both in normal and the twitcher mouse. Transduced neurons, astrocytes and oligodendrocytes were distributed throughout the brain. The transduced LacZ gene, its transcript and protein expression in the brain were maintained for 14 months without decrement. In addition, gene transduction to multiple tissues other than the brain was also detected at low levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study suggests that brain\u2010directed <jats:italic>in utero<\/jats:italic> gene transfer using retrovirus vector may be beneficial to the treatment of lysosomal storage diseases with severe brain damage early in life, such as Krabbe disease. Copyright \u00a9 2005 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.719","type":"journal-article","created":{"date-parts":[[2005,1,31]],"date-time":"2005-01-31T12:46:53Z","timestamp":1107175613000},"page":"540-551","source":"Crossref","is-referenced-by-count":28,"title":["Widespread and highly persistent gene transfer to the CNS by retrovirus vector <i>in utero<\/i>: implication for gene therapy to Krabbe 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