DNase For Prevention Of Reproductive Tract Infections In Pregnancy

DNase 用于预防妊娠期生殖道感染

基本信息

项目摘要

DNase for prevention of reproductive tract infections in pregnancy ABSTRACT Reproductive tract infections (RTI) are of particular relevance during pregnancy and have important implications for maternal and neonatal health. Both bacterial vaginosis and group B Streptococcus are RTI associated with biofilm formation and long-term colonization of the vaginal mucosal surface. We have found that both Gardnerella vaginalis (the major constituent of the vaginal microbiota during bacterial vaginosis) and group B Streptococcus (the leading cause of early-onset sepsis in newborns) form biofilms that contain extracellular DNA and are sensitive to the activity of exogenous DNase. Thus, we hypothesize that an intravaginal DNase gel could decrease the risk of these and potentially other RTI in late pregnancy. Our overall goal is to rigorously evaluate this hypothesis by formulating a lead candidate DNase gel for in vitro and in vivo testing and by leveraging our experience in microbicide acceptability studies to determine potential barriers to the real-world use of such a preventive strategy during pregnancy. In the proposed sequential R21/R33 phased innovation study, the R21 phase will focus on formulation of DNase gel prototypes and evaluation of efficacy against RTI relevant to pregnancy using in vitro and in vivo models and on developing behavioral instruments to study microbicide acceptability in pregnant women. In the R33 phase, we will optimize the lead gel candidate, perform expanded efficacy and toxicology studies in vivo, and use our behavioral instrument to study locally and nationally representative populations of pregnant women. At the conclusion of the two phases, we will have completed a detailed preclinical evaluation of a DNase gel for the prevention of two important RTI in pregnancy and will have performed an assessment of behavioral factors important to the implementation of such a strategy. If a suitable gel advances to the conclusion of the R33 phase with in vivo efficacy and an acceptable toxicologic profile, we will move forward with the eventual goal of human testing.
DNA酶用于预防妊娠期生殖道感染 摘要 生殖道感染(RTI)在怀孕期间特别重要, 对产妇和新生儿健康具有重要影响。细菌性阴道病 和B组链球菌是与生物膜形成和长期 阴道粘膜表面的定植。我们发现加德纳菌 阴道菌(细菌性阴道病期间阴道微生物群的主要组成部分)和 B族链球菌(新生儿早发性脓毒症的主要原因) 生物膜含有细胞外DNA,对外源DNA的活性敏感, DNA酶因此,我们假设阴道内DNA酶凝胶可以降低 这些和潜在的其他RTI在怀孕后期。我们的总体目标是严格 通过配制用于体外和体内试验的主要候选DNA酶凝胶来评估这一假设。 体内试验,并利用我们在杀微生物剂可接受性研究方面的经验, 确定在实际使用这种预防性战略时的潜在障碍, 怀孕在拟议的R21/R33连续阶段创新研究中, 阶段将集中于DNA酶凝胶原型的配制和功效评估 使用体外和体内模型以及在发育过程中, 研究孕妇对杀微生物剂可接受性的行为工具。在R33 阶段,我们将优化领先的凝胶候选产品,扩大疗效, 毒理学研究在体内,并使用我们的行为工具,研究当地和 全国有代表性的孕妇群体。在两人结束时, 阶段,我们将完成一个详细的临床前评估的DNA酶凝胶, 预防两个重要的RTI在怀孕期间,并将进行评估, 行为因素对实施此类策略很重要。如果合适的凝胶 推进R33阶段的结论,具有体内疗效和可接受的 毒理学特征,我们将朝着人类测试的最终目标前进。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Adam Jonathan Ratner其他文献

Adam Jonathan Ratner的其他文献

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{{ truncateString('Adam Jonathan Ratner', 18)}}的其他基金

Capsular serotype in group B Streptococcus colonization and disease
B 组链球菌定植和疾病中的荚膜血清型
  • 批准号:
    10297242
  • 财政年份:
    2021
  • 资助金额:
    $ 47万
  • 项目类别:
Capsular serotype in group B Streptococcus colonization and disease
B 组链球菌定植和疾病中的荚膜血清型
  • 批准号:
    10620312
  • 财政年份:
    2021
  • 资助金额:
    $ 47万
  • 项目类别:
Capsular serotype in group B Streptococcus colonization and disease
B 组链球菌定植和疾病中的荚膜血清型
  • 批准号:
    10424581
  • 财政年份:
    2021
  • 资助金额:
    $ 47万
  • 项目类别:
Spatiotemporal analysis of gene regulatory programs associated with GBS infection during pregnancy
妊娠期GBS感染相关基因调控程序的时空分析
  • 批准号:
    10509389
  • 财政年份:
    2018
  • 资助金额:
    $ 47万
  • 项目类别:
Spatiotemporal analysis of gene regulatory programs associated with GBS infection during pregnancy
妊娠期GBS感染相关基因调控程序的时空分析
  • 批准号:
    10053319
  • 财政年份:
    2018
  • 资助金额:
    $ 47万
  • 项目类别:
Spatiotemporal analysis of gene regulatory programs associated with GBS infection during pregnancy
妊娠期GBS感染相关基因调控程序的时空分析
  • 批准号:
    10290310
  • 财政年份:
    2018
  • 资助金额:
    $ 47万
  • 项目类别:
R21 Orphan nuclear receptors
R21 孤儿核受体
  • 批准号:
    9231663
  • 财政年份:
    2014
  • 资助金额:
    $ 47万
  • 项目类别:
DNase For Prevention Of Reproductive Tract Infections In Pregnancy
DNase 用于预防妊娠期生殖道感染
  • 批准号:
    8843772
  • 财政年份:
    2014
  • 资助金额:
    $ 47万
  • 项目类别:
DNase For Prevention Of Reproductive Tract Infections In Pregnancy
DNase 用于预防妊娠期生殖道感染
  • 批准号:
    8812495
  • 财政年份:
    2014
  • 资助金额:
    $ 47万
  • 项目类别:
DNase For Prevention Of Reproductive Tract Infections In Pregnancy
DNase 用于预防妊娠期生殖道感染
  • 批准号:
    8265110
  • 财政年份:
    2012
  • 资助金额:
    $ 47万
  • 项目类别:

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使用工程益生菌治疗复发性细菌性阴道病
  • 批准号:
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人乳头瘤病毒感染、细菌性阴道病和性伴侣生殖器微生物组之间的相互作用
  • 批准号:
    488743
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    2023
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开发用于治疗细菌性阴道病生物膜的静电纺丝抗菌涂层卫生棉条
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无症状与有症状细菌性阴道病的阴道微环境
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    10666011
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    2023
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持续和分阶段释放抗生素和益生菌支架的 3D 生物打印用于治疗细菌性阴道病
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持续和分阶段释放抗生素和益生菌支架的 3D 生物打印用于治疗细菌性阴道病
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