Receptor-targeting and intracellular disassembly of gene vectors

• Applicant: Professor Dr.-Ing. Manfred Ogris
• Subject Area: Hematology, Oncology
• Term: from 2006 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 22402010

Gene vectors are limited by low efficiency and insufficient target cell specificity. Cellular bottlenecks in the gene transfer process remain to be identified to speed up vector optimization. In the current project, a recently established biochemical targeting strategy will be applied for analysing the gene transfer process in hematopoietic cells. Targeting will combine detargeting (shielding) by bioreversible PEGylation and (re)targeting to specific cell surface receptors. The project will focus on established ligands of hematopoietic cell receptors (transferrin, anti-CD3 or anti-CD117 antibodies) and ligands derived from research network collaborations (such as HSC-specific scFvs). We will evaluate targeted polyplexes based on novel biodegradable polymers, and also provide detargeting/retargeting reagents for viral vector modification to our network partners. Entry pathways and intracellular fate of gene vectors by biooptical studies (flow cytometry, confocal microscopy), use of inhibitors for different cellular pathway, and analysis of cell cycle dependence will be correlated with gene expression to characterize the productive entry pathways. Episomal vectors will be applied for monitoring maintenance of gene expression.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1230: Mechanisms of Gene Vector Entry and Persistence
• Participating Person: Professor Dr. Ernst Wagner