Award details

Dual degradable polycation/DNA polyplexes for gene delivery

Reference	BB/C515855/1
Principal Investigator / Supervisor	Professor Cameron Alexander
Co-Investigators / Co-Supervisors	Dr Silvanand Pennadam, Professor Jon Preece, Professor Leonard Seymour
Institution	University of Nottingham
Department	Sch of Pharmacy
Funding type	Research
Value (£)	144,009
Status	Completed
Type	Research Grant
Start date	01/06/2005
End date	30/09/2007
Duration	28 months

Abstract

This research aims to develop an efficient, fully defined and safe system for delivery of DNA and mRNA to cells based on novel self-assembled polyplexes (colloidal polycation/nucleic acid particles). These polyplexes will display a number of functional attributes that will enhance their efficacy, most notably the combination of stability during the extracellular delivery phase with efficient transfer from endosome to cytoplasm and triggered cytoplasmic degration to maximise release of the nucleic acid at the intended point of cellular delivery. The stability of the polyplexes in extracellular environments will be achieved by maximising the strength of polyelectrolyte binding between nucleic acid and polycation, while endosome escape will be maximised by manipulating pKa and conformational flexibility. The release of nucleic acids from the polyplexes will be accomplished by intracellular activation through the incorporation of reducible disulphides and/or hydrolysable anhydrides within polymer backbone and/or cross-links. In this way we will endow these triggered dual degradable polymer/nucleic acid complexes with the capacity to overcome in vivo degradation prior to delivery with endosomal release properties, enabling the penetration of the polyplexes into the cytoplasm and subsequent release of the nucleic acid. Furthermore, the chemical methodologies we will employ to generate the degradable polyplexes have been designed to permit incorporation of thiol-bearing oligopeptides at the termini of reducible cationic polymers, and this will be used to introduce receptor-specific targeting peptides (eg MQLPLAT) and endosome escape peptides (eg melittin). This project requires multidisciplinary expertise, including organic and polymer chemistry, biomolecular recognition, molecular/cell biology and molecular pharmacology, and will have relevance in fields varying from nanotechnology and pharmaceutical science as well as in the principal discipline of biomedical science. Joint with BB/C515820/1 and BB/C515871/1

Summary

unavailable

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

Associated awards:

BB/C515820/1 Dual degradable polycation/DNA polyplexes for gene delivery

BB/C515871/1 Dual degradable polycation/DNA polyplexes for gene delivery

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