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

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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.