SFEBES2013 Poster Presentations Pituitary (71 abstracts)
Polymersomes-mediated siRNA delivery for states of hormone excess
Georgia Bakirtzi1,4, Giuseppe Battaglia2,3, Giuseppe Battaglia4 & John Newell-Price1
1Academic Unit of Diabetes, Endocrinology and Metabolism, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK; 2The Krebs Institute, University of Sheffield, Western Bank, Sheffield S10 2TN, UK; 3The Centre for Membrane Interactions and Dynamics, University of Sheffield, Western Bank, Sheffield S10 2TN, UK; 4Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
Introduction: Cushing’s disease is a devastating condition associated with a fivefold excess mortality. It is usually due to a small (few mm) benign corticotroph tumour in the pituitary expressing excess pro-opiomelanocortin (POMC), the peptide product of which, ACTH, drives excess secretion of cortisol from the adrenal. There is a clear clinical need for better treatment options.
Background: We have designed, optimized and validated unique siRNAs to POMC and shown highly effective and durable knockdown in vitro and in vivo. Here, we have extended these data to assess the effectiveness of polymersomes, which are biomimetic and polymer-based vesicles, for enhanced delivery of anti-pomc siRNA.
Methods: Polymersomes were formed using the amphiphilic, pH sensitive, PMPC (poly (2-(methacryloyloxy) ethyl phosphorylcholine) – PDPA poly (2-(diisopropylamino)ethyl methacrylate) copolymers. Effectiveness of polymersomes-mediated siRNA delivery was studied in the AtT20 cell line.
Results:: Polymersomes are effective for the delivery of siRNA, supporting their application to deliver anti-pomc siRNA as therapy.
Conclusion: These data further support the potential of a novel epigenetic therapeutic approach for Cushing’s disease.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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