Transduction of bone marrow cells by the AdZ.F(pK7) modified adenovirus demonstrates preferential gene transfer in myeloma cells

Adenoviral vectors can efficiently infect myeloma cell lines, but transduct ion of fresh myeloma cells performed at low multiplicity of infections (MOI s) showed only partial efficacy. The modified adenoviral vector AdZ.F(pK7), through binding of polylysines to heparan sulfate-containing receptors, co uld increase virus adsorption and gene transfer efficiency in myeloma cells , which express heparan sulfate-containing receptors, Thus, we investigated the ability of AdZ.F(pK7) vector to achieve efficient gene transfer in pri mary cultured fresh myeloma cells, Transduction of 16 primary cultured myel oma samples showed that gene transfer was much more efficient with AdZ.F(pK 7) than with control AdZ.F. Both addition of soluble heparin and cell treat ment,vith heparinase I dramatically inhibited gene transfer in myeloma cell s by AdZ.F(pK7) but had no effect with AdZ.F, while addition of recombinant fiber protein inhibited AdZ.F but not AdZ.F(pK7), confirming that AdZ.F(pK 7) gene transfer in myeloma cells is mediated by the targeting of heparan s ulfates, AdZ.F(pK7) transduction of bone marrow cells showed that myeloma c ells and hematopoietic progenitor AC133-, CD34-, and CD33-positive cells we re efficiently transduced at an MOI of 100, but that only myeloma cells wer e significantly transduced at an MOI of 12. Thus, AdZ.F(pK7) vector seems t o be well suited for immunological approaches of gene therapy or bone marro w-purging applications in multiple myeloma.