Efficacy and safety of nanoparticle mediated placental gene therapy in nonhuman primates

纳米颗粒介导的胎盘基因治疗对非人灵长类动物的功效和安全性

基本信息

批准号：
10752759
负责人：
HELEN N JONES
金额：
$ 67.64万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-07 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10752759
关键词：
Address Admission activity Adult Adverse effects Animal Model Animals Aromatase Arteries Basic Science Biology Blood Vessels Cardiovascular Diseases Catheters Chemistry Child Clinical Research Development Diabetes Mellitus Disease Disease model Environment Fetal Growth Fetal Growth Retardation Fetal health Fetus Florida Functional disorder Genetic Giant Cells Goals Health Heart Human Injections Insulin-Like Growth Factor I Intervention Studies Knowledge Lead Life Longevity Macaca mulatta Maternal Health Maternal Physiology Maternal complication Maternal-Fetal Exchange Mediating Metabolic Metabolism Methods Modeling Molecular Morbidity - disease rate Mothers Obesity Operative Surgical Procedures Organ Outcome Pathology Peptides Peripheral Personal Satisfaction Physiological Physiology Placenta Placental Biology Placental Insufficiency Placentation Plasmids Polymers Positioning Attribute Pre-Eclampsia Pregnancy Pregnancy Complications Pregnancy Outcome Pregnant Women Premature Birth Prevention Proteins Public Health Regulation Reporter Research Research Personnel Rest Risk Risk Factors Safety System Testing Therapeutic Therapeutic Intervention Therapeutic Studies Translating Translational Research Treatment Efficacy Universities Uterus Wisconsin Women&apos s Health Work adverse pregnancy outcome experience fetal gene therapy guinea pig model improved in utero in vivo innovation interest model development mortality mouse model multidisciplinary nanocarrier nanoparticle nonhuman primate novel novel strategies novel therapeutic intervention novel therapeutics offspring organ growth pediatric pharmacology peptidomimetics post pregnancy postnatal pregnant premature prenatal stress promoter safety and feasibility therapeutic protein tool transgene expression treatment strategy

Address Admission activity Adult Adverse effects Animal Model Animals Aromatase Arteries Basic Science Biology Blood Vessels Cardiovascular Diseases Catheters Chemistry Child Clinical Research Development Diabetes Mellitus Disease Disease model Environment Fetal Growth Fetal Growth Retardation Fetal health Fetus Florida Functional disorder Genetic Giant Cells Goals Health Heart Human Injections Insulin-Like Growth Factor I Intervention Studies Knowledge Lead Life Longevity Macaca mulatta Maternal Health Maternal Physiology Maternal complication Maternal-Fetal Exchange Mediating Metabolic Metabolism Methods Modeling Molecular Morbidity - disease rate Mothers Obesity Operative Surgical Procedures Organ Outcome Pathology Peptides Peripheral Personal Satisfaction Physiological Physiology Placenta Placental Biology Placental Insufficiency Placentation Plasmids Polymers Positioning Attribute Pre-Eclampsia Pregnancy Pregnancy Complications Pregnancy Outcome Pregnant Women Premature Birth Prevention Proteins Public Health Regulation Reporter Research Research Personnel Rest Risk Risk Factors Safety System Testing Therapeutic Therapeutic Intervention Therapeutic Studies Translating Translational Research Treatment Efficacy Universities Uterus Wisconsin Women&apos s Health Work adverse pregnancy outcome experience fetal gene therapy guinea pig model improved in utero in vivo innovation interest model development mortality mouse model multidisciplinary nanocarrier nanoparticle nonhuman primate novel novel strategies novel therapeutic intervention novel therapeutics offspring organ growth pediatric pharmacology peptidomimetics post pregnancy postnatal pregnant premature prenatal stress promoter safety and feasibility therapeutic protein tool transgene expression treatment strategy

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项目摘要

Project Summary Improved methods for assessing pregnancy well-being, and assessing possible molecular and genetic correlates of poor pregnancy outcomes are currently in development. This knowledge is of limited value, however, without the ability to intervene in troubled pregnancies. The obvious difficult step is to translate knowledge to be gained into placental therapeutics to improve fetal health. Treating the placenta within the pregnant mother has several significant concerns. Placental therapeutics will need to selectively target the placenta to avoid unwanted off-target effects on maternal physiology and to ensure that treating the placenta does not result in inadvertent negative consequences for the fetus. The long-term goal is to establish safe, efficacious and placenta-specific gene therapy in a nonhuman primate in order to establish potential treatment strategies for fetal growth restriction and other pregnancy pathologies in which the placenta plays a role. Furthermore, the development of an organ-specific targeting approach in a nonhuman primate will allow the development of other disease-specific models of pregnancy in an animal model highly translatable to human. The overall objective of this application is to assess the feasibility and safety of a polymer-based nanoparticle that can be taken up by the placental syncytium and result in transgene expression and allow tracking and targeting developments for organ-specific delivery of nanocarriers. The rationale behind this proposal is that it is expected to make significant steps toward a specific, translatable delivery mechanism for therapy in the placenta and to broaden the capabilities of disease modelling in the nonhuman primate. These forward-looking and innovative studies will position University of Florida and University of Wisconsin- Madison investigators to be poised to work towards the ultimate goal, to be able to “treat the placenta”, an ephemeral organ fundamental to our existence, yet exceedingly difficult to address with therapeutic intervention, in the interest of improving pregnancy outcomes, women’s health and lifelong health. This study will also open possibilities for other organ-specific disease models to be developed in the nonhuman primate.

项目摘要改进了评估妊娠健康的方法，并评估可能的分子和遗传目前正在开发妊娠结局不良的相关性。这些知识价值有限，但是，没有能力干预陷入困境的怀孕。显而易见的一步是翻译知识将进入占地治疗以改善胎儿健康。处理胎盘怀孕的母亲有几个重大问题。胎盘疗法将需要选择性地针对胎盘以避免对孕产妇生理的不必要的脱靶影响，并确保治疗胎盘不会对胎儿造成无意的负面后果。长期目标是建立安全，在非人类灵长类动物中有效和多余的基因疗法，以建立潜在的治疗胎儿生长限制和其他怀孕病理的策略，其中plopeta起作用。此外，非人类灵长类动物中特定器官特定的靶向方法的发展将允许在高度翻译为人类的动物模型中开发其他疾病特异性妊娠模型。该应用的总体目的是评估基于聚合物的纳米颗粒的可行性和安全性可以通过胎盘合胞体来处理，并导致转化表达并允许跟踪和针对特定器官特定输送纳米载体的发展。该提议背后的理由是预计将朝着特定的，可翻译的交付机制迈出重大步骤胎盘并扩大非人类灵长类动物中疾病建模的能力。这些前瞻性和创新研究将定位佛罗里达大学和威斯康星大学 - 麦迪逊调查人员被毒死以朝着最终目标努力，能够“治疗多余的人” 短暂的器官是我们存在的基础，但在治疗方面很难解决干预为了改善妊娠结局，妇女健康和终身健康状况。这项研究还将为非人类灵长类动物开发其他器官特异性疾病模型的可能性。