Development of targeted retroviral vectors pseudotyped with the Tupaia paramyxovirus glycoproteins

• Antragsteller: Dr. Christoph Springfeld
• Fachliche Zuordnung: Virologie ; Gastroenterologie
• Förderung: Förderung von 2008 bis 2012
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 61477952

Retroviral vectors are vectors of choice for many gene therapy applications since transduction of target cells results in genomic transgene integration and long term gene expression. An important factor limiting clinical use is the fact that these vectors can not efficiently be targeted to designated cells. We propose to generate targeted retroviral vectors pseudotyped with the two Tupaia Paramyxovirus (TPMV) glycoproteins, the hemagglutinin (H) and the fusion (F) protein. We have previously shown that the TPMV glycoproteins can be targeted to normally non-permissive cells by displaying single-chain antibodies on the H protein that recognize cell surface antigens on target cells, e.g. CD20 or carcinoembryonic antigen (CEA). The novel vectors will combine the excellent targeting possibilities of paramyxovirus glycoproteins with the advantage of transgene integration provided by retroviruses. Based on previously reported work for a related paramyxovirus, we will generate a panel of TPMV glycoproteins with various modifications of their cytoplasmic tails. We will identify the modified proteins that support incorporation into retroviral vectors and characterize the novel vectors in vitro. Finally, we will examine the efficacy of cancer cell transduction with therapeutic genes in vivo in different mouse tumor models. Fully targeted retroviral vectors would represent a major advance in gene therapy with a wealth of clinical applications.

• DFG-Verfahren: Sachbeihilfen