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Karen Kræmmer Schelde: RNA-based drugs for the lung and how to overcome the mucous barrier

PhD defence, Wednesday 13 September 2017. Karen Kræmmer Schelde.

Karen Kræmmer Schelde
Confocal microscopy image of the murine bronchiolar wall after administration of chitosan/fluorescently-labelled siRNA nanoparticles. Nuclei are stained red, and the fluorescently-labelled siRNA is stained green. The green signal indicates that the siRNA is captured in the mucous on the apical (luminal) side of the epithelium.

During her PhD studies, Karen Kræmmer Schelde has been conducting research on how to deliver nucleotide-based drugs to the lungs. She worked on cellular lung models for the study of nanoparticles generated from the sugar chitosan and nucleotide-based drugs as siRNA. siRNAs as a treatment are able to specifically inhibit translation of mRNA into protein, and thereby inhibit a specific gene expression. Other nucleotide-based drugs, as gapmers, have also been tested for delivery to lung cells. Karen Kræmmer Schelde has used pig and mice animal models to show the nebulising effect and distribution/uptake of the nanoparticles in the lungs. Nanoparticles made from chitosan are seen to be captured in the mucous in the lung and thereby increase the retention time for the drug delivery. This system could be very efficient for cystic fibrosis patients, who have a thicker and more rigid mucous layer and therefore, the RNA-therapy has been directed at treating cystic fibrosis.

The PhD degree was completed at the Interdisciplinary Nanoscience Center (iNANO), Science and Technology, Aarhus University.

This résumé was prepared by the PhD student.

Time: Wednesday, 13 September 2017 at 13.15
Place: Building 1593, room 012, the Lecture Theatre, iNANO House, Gustav Wieds Vej 14, Aarhus University, 8000 Aarhus C.
Title of dissertation: Delivery of nucleotide-based drugs for gene silencing in pulmonary epithelia
Contact information: Karen Kræmmer Schelde, e-mail: kkschelde@inano.au.dk, tel.: +45 4076 6414
Members of the assessment committee:
Associate Professor Jeffrey M. Beekman, University Medical Center Utrecht, the Netherlands
Senior Hospital Physician, Doctor of Medicine, Medical Specialist in Paediatrics, Paediatric Pulmonology, Tacjana Pressler, Department of Paediatrics and Adolescent Medicine, Juliane Marie Centre, Rigshospitalet
Professor Daniel Otzen (chair), iNANO and Department of Molecular Biology and Genetics, Aarhus University

Main supervisor:
Professor Jørgen Kjems, iNANO and Department of Molecular Biology and Genetics, Aarhus University
Associate Professor Jørgen Eskild Petersen, Department of infectious diseases, Aarhus University Hospital
Language: The PhD dissertation will be defended in English

The defence is public.
The dissertation is available for reading at the Graduate School of Science and Technology/GSST, Ny Munkegade 120, building 1520, rooms 128-134, 8000 Aarhus C.