Development of a cell-specific transfection system based on ligand-dependent endocytosis

• Applicant: Dr. Iring Heisler
• Subject Area: Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2005 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5452020

Targeted gene therapy requires a cell- and / or a tissue-specific expression or down-regulation of therapeutic genes. Since the development of RNA interference (RNAi) as method for downregulation of target genes by siRNA there is increasing interest in its application in gene therapy. The main obstacle for the applicability of siRNA as a small molecule drug is its delivery into the cytosol across the cell membrane in vivo. Within the cytosol it can enter the RNAi pathway and guides the sequence-specific target mRNA degradation. Most cells including macrophages only take up siRNAs by the addition of transfection reagents or by using hydrodynamic high pressure resulting in damages within the plasma membrane. In contrast to siRNAs viral vectors are able to efficiently deliver nucleic acids into a relatively specific cell population but there are many problems associated with viral vectors, which restrict their clinical application. The objective of this project is to develop a transfection system for the delivery of exogenous genes and siRNAs in a cell-specific manner. This will be achieved by a highly specific mechanism: the active compound (DNA or siRNA) is coupled via a nucleic acid-binding property that is fused to a target cell-specific ligand by a multi-functional molecular adapter. The adapter has been already developed in our research group. The efficiency of nucleic acid delivery is intended to be enhanced by saponins as additive.

• DFG Programme: Research Grants