A Novel Herpes Vector for the High-Efficiency Transduction of Normal and Malignant Human Hematopoietic Cells

作者: Dagmar Dilloo , Donna Rill , Claire Entwistle , Michael Boursnell , Wanyun Zhong

DOI: 10.1182/BLOOD.V89.1.119.119_119_127

关键词:

摘要: Herpes simplex viruses (HSVs) would offer numerous advantages as vectors for gene transfer, but yet they have not proved capable of transducing hematopoietic cells. Using a genetically inactivated form HSV that is restricted to single cycle replication (disabled single-cycle virus, [DISC-HSV]), we transduced normal human progenitor cells and primary leukemia blasts with efficiencies ranging from 80% 100%, in the absence growth factors or stromal support. Toxicity was low, 70% 100% surviving transduction process. Peak expression transferred genes occurred at 24 48 hours after DISC-HSV vector, declining near background levels by 14 days. Despite this limitation, sufficient protein produced inserted permit consideration vector applications which transient adequate. One example transfer immunostimulatory genes, generate immunogens. Thus, murine A20 encoding granulocyte-macrophage colony-stimulating factor were able stimulate potent antitumor response mice, even against pre-existing leukemia. The exceptional ability should therefore facilitate genetic manipulation malignant biological clinical investigation.

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