Projects per year
Antimicrobial resistance to traditional antibiotics is a crucial challenge of medical research. Oligonucleotide therapeutics, such as antisense or Transcription Factor Decoys (TFDs), have the potential to circumvent current resistance mechanisms by acting on novel targets. However, their full translation into clinical application requires efficient delivery strategies and fundamental comprehension of their interaction with target bacterial cells. To address these points, we employed a novel cationic bolaamphiphile that binds TFDs with high affinity to form self-assembled complexes (nanoplexes). Confocal microscopy revealed that nanoplexes efficiently transfect bacterial cells, consistently with biological efficacy on animal models. To understand the factors affecting the delivery process, liposomes with varying compositions, taken as model synthetic bilayers, were challenged with nanoplexes and investigated with Scattering and Fluorescence techniques. Thanks to the combination of results on bacteria and synthetic membrane models we demonstrate for the first time that the prokaryotic-enriched anionic lipid Cardiolipin (CL) plays a key-role in the TFDs delivery to bacteria. Moreover, we can hypothesize an overall TFD delivery mechanism, where bacterial membrane reorganization with permeability increase and release of the TFD from the nanoplexes are the main factors. These results will be of great benefit to boost the development of oligonucleotides-based antimicrobials of superior efficacy.
|Publication status||Published - 25 Jan 2017|
- Norwich Medical School - Professor of Nanomedicine
- Gastroenterology and Gut Biology - Member
Person: Research Group Member, Academic, Teaching & Research
- 1 Finished
DNA-TRAP Delivery of Nucleic Acid-Based Theraputics for the TReatment of Antibiotic-Resistant Pathogens.
Morris, C., Baldelli Bombelli, F., Mcarthur, M., Wheeler, G., Giorgetti, M., Ruiz Estrada, G., Ruyra Ripoll, A., Saide, K. & Sitia, L.
1/10/13 → 30/09/17
- 35 Citations (Scopus)
- 1 Article
Cationic liposomal vectors incorporating a bolaamphiphile for oligonucleotide antimicrobialsMamusa, M., Sitia, L., Barbero, F., Ruyra, A., Díaz Calvo, T., Montis, C., Gonzalez-Paredes, A., Wheeler, G. N., Morris, C. J., McArthur, M. & Berti, D., Oct 2017, In: Biochimica et Biophysica Acta (BBA) - Biomembranes. 1859, 10, p. 1767–1777 11 p.
Research output: Contribution to journal › Article › peer-reviewOpen AccessFile21 Citations (Scopus)17 Downloads (Pure)