Mimicking Nature to deliver plasmid DNA and RNAi molecules for in vivo applications
Our project
(Figure above: Novel glycosaminoglycan-based intracellular delivery strategies of plasmid DNA and RNAi drugs.)
Cellular delivery of nucleic acid drugs has been at the forefront of research for many years. Even though we could delivery molecules inside the cells, it remains trapped within the endolysosomal compartments. With well-known lipid-based delivery, only 1-2% of the cargo molecules reaches the target site. Our ambition is to identify novel methods by mimicking Nature to develop novel delivery strategies. We have recently shown that nanoparticles coated with glycosaminoglycans can control plasmid release from the endosome and improve transfection efficiency. Such delivery carriers are promising owing to their unique tumour targeting ability (e.g. HA targets CD44 receptor). We have also recently developed the first non-cationic non-viral siRNA delivery methods by exploiting naturally occuring Van der Waal’s and H-bonding interactions. These methods will provide next-generation transfection reagent that does not rely on electrostatic interactions between cationic polymers and the phosphate backbone of DNA.
Publications
- Paidikondala, M.; Rangasami, V. K.; Nawale, G. N.; Casalini, T.; Perale, G.; Kadekar, S.; Mohanty, G.; Salminen, T.; Oommen, O. P.; Varghese, O. P. An Unexpected Role of Hyaluronic Acid in Trafficking siRNA Across the Cellular Barrier: The First Biomimetic, Anionic, Non-Viral Transfection Method. Angew. Chem. Int. Ed. 2019, 58, 2815-2819. https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201900099
- Paidikondala, M.; Kadekar, S.; Varghese, O. P. Innovative Strategy for 3D Transfection of Primary Human Stem Cells with BMP-2 Expressing Plasmid DNA: A Clinically Translatable Strategy for Ex Vivo Gene Therapy. Int. J. Mol. Sci. 2019, 20, 56. http://www.mdpi.com/1422-0067/20/1/56
- Paidikondala, M.; Nawale, G. N.; Varghese, O. P. Insights into siRNA Transfection in Suspension: Efficient Gene Silencing in Human Mesenchymal Stem Cells Encapsulated in Hyaluronic Acid Hydrogel. Biomacromolecules 2019. https://doi.org/10.1021/acs.biomac.8b01712
- Yan, H.; Oommen, O. P.; Yu, D.; Hilborn, J.; Qian, H.; Varghese, O. P. Chondroitin Sulfate-Coated DNA-Nanoplexes Enhance Transfection Efficiency by Controlling Plasmid Release from Endosomes: A New Insight into Modulating Nonviral Gene Transfection. Adv. Funct. Mater. 2015, 25, 3907-3915. https://onlinelibrary.wiley.com/doi/abs/10.1002/adfm.201500695