Transcriptional targeting of a lentiviral vector f or myeloma gene therapy

David Dingli, Rosa Maria Diaz, Lie Zhang, Richard Vile, Stephen J. Russell

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Multiple myeloma is a malignant disorder of plasma cells. Despite the use of ligh dose combination chemotherapy and stem cell support, it remains incurable. Resistance to chemotherapy in part due to the slow proliferative rate of the malignant plasma dells. Lentiviruses can infect non-dividing cells; thus they may be attractive vectors for a gbnebased therapy in this disease. Specific transgene expression might be achieved eithelr by targeting entry (targeted delivery) of the vector or by restricting expression of the transgene to the cell of interest (transcriptional targeting). We have developed lentiviral vectors that express transgenes preferentially in myeloma cell lines. Our constructs are based on selfinactivating (SIN) lentiviral vectors. Transgene expression (enhanced green fluorescent protein, eGFP) is driven in these vectors by immunoglobulin promoter and enhancer elements. The promoter contains a consensus TATA box and an octameric motif known to be specific for immunoglobulin expression. Expression from this promoter is enhanced by the presence of the SOObase pair 3' Kappa light chain enhancer. eGFP expression was evaluated by flow cytometry. The VSV-pseudotyped lentiviral vectors infect myeloma cell lines efficiently and show specific, high-level eGFP expression in vitro (MM1, RPMI 8226 and ARH77). Expression is strongly inhibited in T cell (Jurkat), myeloid cell (K562) or non-hemopoietic cell lines (HT1080 and Mel 624). High level GFP expression was obtained in all cell lines infected with a control lentiviral vector driven by a CMV promoter/enhancer. Conclusion: HIV based vectors can be transcriptionally targeted to give specific, high level transgene expression in myeloma cells. With the introduction of cytotoxic genes, such vectors may potentially be used to treat multiple myeloma.

Original languageEnglish (US)
Pages (from-to)158a
JournalBlood
Volume96
Issue number11 PART I
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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