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

利用瞬时基因转移至子宫内膜开发针对植入失败患者的基因治疗模型

• 批准号: 15390505
• 负责人: KIMURA Tadashi
• 金额: $ 7.68万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390505/
• 关键词: endometrium; implantation; in vivo gene transfer; HVJ-E vector; NF-κB; decoy; デコイ; NFKappaB; 生体内一過性遺伝子導入・発現系; NFkappaβ

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.

在尝试了几种方法后，我们建立了利用来自灭活仙台病毒包膜的HVJ-E载体在体内将基因转移到小鼠妊娠子宫内膜中的高效方案（Mol. Reprod 2003：9;603）。我们注意到多能转录因子NF-κB在着床期小鼠子宫内膜上皮中被激活（Am J Reprod Immunol 2004：51;16）。因此，我们将IκB cDNA的显性负突变体转入小鼠子宫内膜，其抑制NF-κB活化不到一半。这种处理导致着床延迟1天，而不影响妊娠过程（BBRC 2004：321;886）。NF-κB decoy也有类似的结果。我们发现NF-κB B是决定着床时机的关键因素。该方案提供了植入失败的基因治疗的基本知识，而不干扰正常的妊娠过程。

项目成果

Alteration of the timing of implantation by in vivo gene transfer : delay of Implantation by suppression of nuclear factor kB activity and partial by leukemia inhibitory factor

通过体内基因转移改变植入时间：通过抑制核因子kB活性和部分通过白血病抑制因子延迟植入

• 发表时间: 2004
• 期刊: Biochem Bioph Res Co 321
• 作者: H.Nakamura;T.Kimura;et al.
• 通讯作者: et al.

T.Kimura., et al.: "Molecular regulation of the oxytocin receptor in peripheral organs"J Mol Endocrinol. 30. 109-115 (2003)

T.Kimura. 等人：“外周器官中催产素受体的分子调节”J Mol Endocrinol。

K.Temma., K.Shimoya., Q.Zhang., T.Kimura., et al.: "Effects of 4-hydroxy-2-nonenal (HNE), a marker of oxidative stress, on the cyclooxygenase (COX)-2 of human placenta in chorioamnionitis"Mol Hum Reprod. 10(3). 167-171 (2004)

K.Temma.、K.Shimoya.、Q.Zhang.、T.Kimura. 等人：“氧化应激标志物 4-羟基-2-壬烯醛 (HNE) 对环氧合酶 (COX) 的影响

Alteration of the timing of implantation by in vivo gene transfer:: delay of implantation by suppression of nuclear factor κB activity and partial rescue by leukemia inhibitory factor

• DOI: 10.1016/j.bbrc.2004.07.045
• 发表时间: 2004-09-03
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Nakamura, H;Kimura, T;Murata, Y
• 通讯作者: Murata, Y

Highly efficient and minimally invasive in-vivo gene transfer to the mouse uterus using haemagglutinating

利用血凝法将基因高效、微创地转移至小鼠子宫

• 发表时间: 2003
• 期刊: Mol Hum Reprod 9
• 作者: H.Nakamura.;T.Kimura.;et al.
• 通讯作者: et al.