TARGETED GENE VECTOR: Targeted vectors for cancer gene therapy: receptor and transcriptional targeting of retroviral, lentiviral and adenoviral vectors.

• Research unit: EU RFP
• Project number: 00.0218

Key words (English)

Retroviral vectors; lentiviral vectors; adenoviral vectors

Alternative project number (English)

EU project number: QLK3-1999-00364

Research programs (English)

EU-programme: 5. Frame Research Programme - 1.1.3 The 'cell factory'

Short description (English)

See abstract

Further information (English)

Full name of research-institution/enterprise:
Université de Genève
Département de Génétique et Microbiologie
CMU

Partners and International Organizations (English)

Coordinator: Université Pierre et Marie Curie (F)

Abstract (English)

Our laboratory developed lentiviral vectors, a new gene delivery system that offers great promises for human gene therwpy. Within the framework of this european project, we proposed to develop further and optimize lentiviral vector-based techniques for the transfer of genes into the liver. Over the last year we demonstrated that a so-called third-generation HIV-derived vector system can govern the efficient delivery, integration and stable expression of a transgene into primary human hepatocytes in the complete absence of cell division. We also showed that rat and mouse hepatocytes are significantly resistant to HIV vector-mediated transduction due to a block in the immediate-early phase of infection, an important shortcoming of rodent models for the preclinical assessment of this therapeutic tool. We finally described a methodology that allows very high rates of transduction through minimal in vitro manipulation, in which hepatocytes are kept in suspension and re-implanted within a few hours of harvest with a fully preserved engraftment potential. These results have immediate implications for the treatment of liver diseases via the transplantation of genetically modified hepatocytes, an approach that could be applied to a number of hereditary and acquired hepatic disorders.

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 00.0218