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

Sonya Frazier, Hannah Morgan, Martin McBride, Angela Bradshaw, Helen Mulvana, Delyth Graham

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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.

Original languageEnglish
Title of host publication2019 IEEE International Ultrasonics Symposium, IUS 2019
Place of PublicationPiscataway, N.J.
Pages1551-1555
Number of pages5
ISBN (Electronic)9781728145969
DOIs
Publication statusPublished - 9 Dec 2019
Event2019 IEEE International Ultrasonics Symposium: IEEE UFFC - SECC, Glasgow, United Kingdom
Duration: 6 Oct 20199 Oct 2019
https://attend.ieee.org/ius-2019/

Publication series

NameIEEE International Ultrasonics Symposium, IUS
Volume2019-October
ISSN (Print)1948-5719
ISSN (Electronic)1948-5727

Conference

Conference2019 IEEE International Ultrasonics Symposium
Abbreviated titleIUS 2019
CountryUnited Kingdom
CityGlasgow
Period6/10/199/10/19
Internet address

Keywords

  • gene therapy
  • microbubbles
  • microRNAs
  • placenta
  • preeclampsia
  • ultrasound

Cite this

Frazier, S., Morgan, H., McBride, M., Bradshaw, A., Mulvana, H., & Graham, D. (2019). Ultrasound and microbubble gene delivery for targeting altered placental microRNAs in preeclampsia. In 2019 IEEE International Ultrasonics Symposium, IUS 2019 (pp. 1551-1555). (IEEE International Ultrasonics Symposium, IUS; Vol. 2019-October).. https://doi.org/10.1109/ULTSYM.2019.8926052