Development of gene therapy model for implantation failure patients using transient gene transfer to uterine endometrium

在尝试了多种方法后，我们建立了一种高效的方法，利用仙台病毒灭活包膜衍生的HVJ-E载体将基因转移到小鼠妊娠子宫内膜（Mol Hum repd 2003:9;603）。我们注意到多电位转录因子NF-κB在着床期小鼠子宫内膜上皮中被激活（Am J repd Immunol 2004:51;16）。因此，我们将i -κB cDNA的显性阴性突变体转移到小鼠子宫内膜，其抑制NF-κB激活的作用不到一半。这种治疗导致着床延迟1天而不影响妊娠进程（BBRC 2004:321;886）。NF-κB诱饵也有类似的结果。我们发现NF-κB是决定着床时机的关键因素。该方案提供了基因治疗植入失败的基本知识，而不影响正常的妊娠过程。

After trying several methods, we established high efficient protocol for in vivo gene transfer into mouse pregnant endometrium using HVJ-E vector, which derived from inactivated Sendai virus'envelope (Mol Hum Reprod 2003:9;603). We noticed multipotential transcription factor, NF-κB is activated in mouse endometrial epithelium at the implantation period (Am J Reprod Immunol 2004:51;16). We therefore transfer dominant negative mutant of IκB cDNA into murine endometrium, which inhibitied NF-κB activation less than half. This treatment induced implantation delay for 1 day without disturbing the course of pregnancy (BBRC 2004:321;886). NF-κB decoy gave similar result. We found that NF-κB is crucial factor to determine the timing of implantation. This protocol provides basic knowledge for gene therapy for implantation failure without disturbing the normal course of pregnancy.