Antisense RNA Inhibition of Hematopoietic Growth Factor Production

Vectors that generate antisense RNA targeted to granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA sequences were constructed using a strong viral promoter and a T cell-specific control element from the human CD2 gene. Stably transfected lymphoid clones expressing antisense RNA were tested for their ability to synthesize GM-CSF in response to stimulation with phorbol 12-myristate 13-acetate (TPA) and ionomycin. At early time points (4 and 8 hr) following stimulation, mean GM-CSF production by clones expressing antisense RNA was 10% the mean of control clones (p less than 0.001). Analysis of mean log data for 15 antisense clones demonstrated that GM-CSF production remained depressed at 12 and 24 hr time points, averaging 37% of that of the control clones (p less than 0.01). We conclude that antisense inhibition of growth factor production may be an effective strategy to investigate the role of specific growth factors in hematopoiesis in vivo in transgenic mice.