In-vivo Non-viral Placental Gene Modulation
Date
2020
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Abstract
The placenta is critical to fetal development, health during pregnancy and the long-term health of the offspring because the placenta contributes to controlling the intra-uterine environment but placental function is still not completely understood. Currently, the lack of minimally invasive gene modulation methods for placental genes limits the types of investigations that can be performed. Safe and efficient gene therapy to the placenta opens a myriad of possibilities. Additionally, the link(s) between placental function, the intrauterine milieu, fetal health and disease development later in life is poorly understood. In this dissertation I demonstrate, the delivery of gene cassettes non-virally by utilizing ultrasound cavitated microbubbles carrying plasmid DNA as well as the ability to modify the placental genetics by piggyBac mediated transgenesis. In previous studies, these methods have been used to modulate gene expression in a variety of different organs but never in the placenta. The transgene cassette is trophoblast specific and spatial targeting is achieved by use of an unfocused ultrasound transducer. This could have applications in the treatment of fetal growth restriction, intra-uterine growth restriction, fetal overgrowth and pre-eclampsia.
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Molecular biology, Cellular biology, Developmental biology, gene delivery, placenta, pregnancy, sonoporation, transgenic, ultrasound
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109 pages
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