Investigating the use of autonomously replicating plasmid vectors for cystic fibrosis gene therapy

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Project objective

The aim of the research project is to study the use of plasmids containing mammalian origins of replication for gene therapy of cystic fibrosis (CF). Previous reports from Dr. College's group have demonstrated the feasibility of using non-replicating plasmid/liposome complexes for CF gene therapy in vivo. Replicating versus non-replicating plasmids containing different reporter genes or the CFTR gene will be tested to assess whether autonomous replication improves the efficiency and duration of gene expression in vitro and in vivo. The test system will be optimised using plasmids containing viral origins of replication but since plasmids that encode viral transforming proteins are not suitable for human gene therapy trials, we will also generate plasmids that contain some of the recently identified mammalian origins of replication. Plasmid replication assays will be performed in vitro using murine and human cultured epithelial cells. Plasmids will be introduced into cells by electroporation, liposomes or calcium phosphate precipitation. Once the replicating plasmids have been tested for their relative transfection and expression efficiencies in vitro, they will be tested in vivo for correction of the C1- channel defect in CF mice.

Original text from CORDIS.

Participants

• Aristotle University of Thessaloniki · ThessalonikiCoordinatorGreece

Links

• View on CORDIS