Z Gastroenterol 2025; 63(08): e378
DOI: 10.1055/s-0045-1810651
Abstracts | DGVS/DGAV
Freie Vorträge

Screening of adenoassociated virus serotypes to transduce gastric smooth muscle cells for optogenetic stimulation

Authors

  • M Vogt

    1   Universitätsmedizin Göttingen, Institut für Herz- und Kreislaufphysiologie, Göttingen, Deutschland

  • J Riebeling

    1   Universitätsmedizin Göttingen, Institut für Herz- und Kreislaufphysiologie, Göttingen, Deutschland
    2   Universitätsmedizin Göttingen, Allgemein-, Viszeral- und Kinderchirurgie, Göttingen, Deutschland
    3   Universitätsmedizin Göttingen, Else Kröner Fresenius Center for Optogenetic Therapies, Universitätsmedizin Göttingen, Göttingen, Deutschland, Göttingen, Deutschland

  • D Zipf

    1   Universitätsmedizin Göttingen, Institut für Herz- und Kreislaufphysiologie, Göttingen, Deutschland

  • L-C Conradi

    2   Universitätsmedizin Göttingen, Allgemein-, Viszeral- und Kinderchirurgie, Göttingen, Deutschland
    3   Universitätsmedizin Göttingen, Else Kröner Fresenius Center for Optogenetic Therapies, Universitätsmedizin Göttingen, Göttingen, Deutschland, Göttingen, Deutschland

  • M Ghadimi

    2   Universitätsmedizin Göttingen, Allgemein-, Viszeral- und Kinderchirurgie, Göttingen, Deutschland
    3   Universitätsmedizin Göttingen, Else Kröner Fresenius Center for Optogenetic Therapies, Universitätsmedizin Göttingen, Göttingen, Deutschland, Göttingen, Deutschland

  • R Patejdl

    4   Health and Medical University Erfurt, Department Medizin, Erfurt, Deutschland

  • T Bruegmann

    1   Universitätsmedizin Göttingen, Institut für Herz- und Kreislaufphysiologie, Göttingen, Deutschland
    3   Universitätsmedizin Göttingen, Else Kröner Fresenius Center for Optogenetic Therapies, Universitätsmedizin Göttingen, Göttingen, Deutschland, Göttingen, Deutschland
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    Background: Gastroparesis is characterized by severely impaired gastric emptying without physical obstruction, causing symptoms such as nausea, vomiting and epigastric pain. Unfortunately, no treatment option to reliably restore gastric emptying exists by date. In Optogenetics, light-sensitive proteins are overexpressed in the target cells by genetic manipulation, which enables targeted stimulation with high spatial and temporal resolution. We previously showed that direct optogenetic stimulation of murine gastric smooth muscle cells (SMCs) with UV or blue light can induce force and increase intragastric pressure in transgenic mice expressing Neuropsin (hOPN5) or Channelrhodopsin 2 (ChR2). As the next step towards clinical translation, an efficient gene delivery vector is needed to express optogenetic proteins in gastric SMCs in vivo.

    Aim of the project: Adeno-associated viruses (AAVs) are a promising tool in gene therapy and already entered clinics. We compared the transduction efficiency of known AAV serotypes in isolated murine gastric SMC.

    Methods: Gastric SMC were isolated from CD-1 wild type mice and known AAV serotypes (1, 2, 3, 5, 6, 7, 8, 9, 10, eB, and PHP) as well as the novel AAV2.5 were systematically tested. Therefor SMC were incubated with increasing doses of each AAV. After 6 days, the transduction efficiency was analyzed by fluorescence microscopy.

    Results: Three different capsid variants (AAV2.5, AAV2, AAV1 and AAV6) enabled expression rates above 40%. Compared to any other known AAV the transduction efficiency of AAV2.5 was more than one order of magnitude better (indicated by log 10 (EC50): AAV2: 8,08±0,08 (n=3) and AAV2.5: 6,89±0,12 (n=3).

    Conclusion: We identified AAV2.5 as a potent capsid for gene transfer into gastric SMCs. As a next step, we will perform this screen analogously in human gastric SMC before the gene transfer will be tested in vivo in mice.

    Präsentiert in der Sitzung: Neurogastroenterologie

    Donnerstag, 18. September 2025, 09:30 – 11:00, Saal 3


     

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    Artikel online veröffentlicht:
    04. September 2025

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