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Intracellular trafficking of polymeric viral mimetics designed for intracytoplasmic delivery of gene and oligonucleotide therapeutics

Reference	E12524
Principal Investigator / Supervisor	Professor Ruth Duncan
Co-Investigators / Co-Supervisors	Professor Stephen Brocchini, Dr Simon Richardson
Institution	Cardiff University
Department	Welsh School of Pharmacy
Funding type	Research
Value (£)	320,509
Status	Completed
Type	Research Grant
Start date	01/11/1999
End date	01/10/2004
Duration	59 months

Abstract

Polyamidoamines (PAAs) are biocompatible, non-hepatotropic components of polymeric vectors designed for intracytoplasmic delivery. As they display pH-triggered membrane lysis (they promote endosomal/lysosomal rupture in vitro and in vivo) PAAs can act as a synthetic alternative to natural fusogenic peptides that promote cytosolic access. In this study the intracellular trafficking of second generation radiolabelled PAA-containing vectors will be monitored using quantitative subcellular fractionation and fluorescence microscopy first in vitro and in tissues following in vivo administration. Systematically, PAA conjugates containing peptidyl cell organelle-locating sequences will be synthesised to (1) maximise endosomal escape and to (2) investigate the potential for organelle selective targeting. Effect on transfection efficiency in vitro and in vivo will be used as a pharmacological correlate in this basic structure-activity study.

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

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