Development of a non-viral episomal vector system enabling tissue-specific replication

• Applicant: Privatdozent Dr. Armin Baiker
• Subject Area: Hematology, Oncology
• Term: from 2006 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 22729010

One of the major factors for safe and reproducible gene delivery is the autologous and tissue-specific expression of the transgene. In most cases, tissue-specific expression in vivo is achieved by vectors that explicitly deliver the gene of interest into a distinct cell type or tissue by the utilization of specific receptors. Here we propose the generation of non-viral episomally replicating vectors that are able to tissue-specifically replicate. One of the applicants (A.B.) was mainly involved in the development of the first small nonviral, episomally replicating vector system based on a chromosomal scaffold/matrix attachment region sequence (S/MARs). The episomal replication of the prototype vector pEPI-1 depends ultimately on a transcription unit that is starting from the constitutively expressed Cytomegalovirus immediate early promoter (CMV-IEP) and that is extending into a S/MARs. In this project, we will construct a novel pEPI-1 derived vector generation which is able to tissue-specifically replicate based on S/MARs and autologous, tissue-specific transcription units, and we will subsequently test these novel prototype vectors in vitro and in vivo.

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