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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2510-2518.
Prepublished online as a Blood First Edition Paper on November 30, 2004; DOI 10.1182/blood-2004-08-3052.
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Submitted August 6, 2004
Accepted November 2, 2004
Inhibiting primary effusion lymphoma by lentiviral vectors encoding short hairpin RNA
Andrew Godfrey, John Anderson, Antigoni Papanastasiou, Yasu Takeuchi, and Chris Boshoff*
Cancer Research UK Viral Oncology Group, University College London, Wolfson Institute for Biomedical Research, London, United Kingdom
Unit of Molecular Haematology and Cancer Biology, University College London, Institute of Child Health, London, United Kingdom
Windeyer Institute for Medical Sciences, University College London, London, United Kingdom
* Corresponding author; email: c.boshoff{at}ucl.ac.uk.
We use lentiviral delivered RNA interference (RNAi) to inhibit the growth of a model of primary effusion lymphoma (PEL) in vitro and in vivo. RNAi is a phenomenon allowing the sequence specific targeting and silencing of exogenous and endogenous gene expression and is being applied to inhibit viral replication both in vitro and in vivo. We show that silencing of genes believed to be essential for the KSHV latent life cycle (the oncogenic cluster) has a varied effect in PEL cell lines cultured in vitro, however concomitant silencing of the viral cyclin (vcyclin) and viral FLICE inhibitory protein (vFLIP) caused efficient apoptosis in all PEL lines tested. We demonstrate that in a murine model of PEL, lentiviral mediated RNA interference both inhibits development of ascites and can act as a treatment for established ascites. We also show that the administered lentiviral vectors are essentially limited to the peritoneal cavity, which has advantages for safety and dosage in a therapeutic setting. This shows the use of lentiviral mediated RNA interference in vivo as a potential therapeutic against a virally driven human cancer.
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