Ultrasound and microbubble gene delivery for targeting altered placental microRNAs in preeclampsia

Frazier, Sonya and Morgan, Hannah and McBride, Martin and Bradshaw, Angela and Mulvana, Helen and Graham, Delyth; (2019) Ultrasound and microbubble gene delivery for targeting altered placental microRNAs in preeclampsia. In: 2019 IEEE International Ultrasonics Symposium, IUS 2019. IEEE International Ultrasonics Symposium, IUS . IEEE Computer Society Press, GBR, pp. 1551-1555. ISBN 9781728145969 (https://doi.org/10.1109/ULTSYM.2019.8926052)

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Abstract

Ultrasound (US) and microbubble (MB) gene delivery has attracted growing interest as a clinically applicable gene therapy (GT). Though preclinical studies have investigated the system in various tissues, there is limited research in targeting the placenta. This is a potential therapeutic strategy for preeclampsia (PE), which has an underlying genetic basis and ineffective management strategies. Differentially expressed placental microRNAs (miRNAs) in PE may represent suitable targets for GT. Microbubbles (SonoVue) and plasmid (pGL3 or pGL4.13) were administered systemically to CD1 mice, followed by exposure of the heart to US (H14, 1.8 M.I., 1cm focal depth, 2 minutes), using Siemens Acuson Sequoia-512 system and 15L8 probe. Luciferase assays were performed to evaluate gene transfection. Significantly differentially expressed placental miRNAs in PE patients were identified as candidates based on detection by three or more screening studies. Expression of candidate miRNAs was measured by qRT-PCR in PE rat model placentas. In trial 1, low levels of luciferase activity were detected in the heart of treatment mouse 1, 2 and 3. In trial 2, luciferase activity was evident in the atria of treatment mouse 2. In trial 3, higher luciferase activity was detected in the ventricles of the treatment mouse and activity was also detected in the atria. The literature review identified eight candidate miRNAs. MiR-223 (1.46-fold increase) and miR-181a (0.81-fold decrease) were significantly differentially expressed in PE rat model placentas. MiR-223 and -181a may represent targets for US and MB gene delivery. Future studies will apply the US and MB gene delivery protocol for translation to targeting the placenta in our PE rodent model.

ORCID iDs

Frazier, Sonya, Morgan, Hannah, McBride, Martin, Bradshaw, Angela, Mulvana, Helen ORCID logoORCID: https://orcid.org/0000-0002-5058-0299 and Graham, Delyth;
  • Item type:Book Section
    ID code:71717
    Dates:
    Date
    Event
    9 December 2019
    Published
    6 October 2019
    Accepted
    Notes:© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.
    Subjects:Technology > Engineering (General). Civil engineering (General) > Bioengineering
    Department:Faculty of Engineering > Biomedical Engineering
    Depositing user: Pure Administrator
    Date deposited:06 Mar 2020 12:02
    Last modified:11 Nov 2024 15:20
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/71717
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