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Expression of human IL‐1 α after intramarrow gene transfer into healthy non‐human primate by adenoviral vector
Author(s) -
Bécard Nicolas,
Revel Thierry,
Sorg Tania,
Dormont Dominique,
Le Grand Roger
Publication year - 2005
Publication title -
journal of medical primatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.31
H-Index - 42
eISSN - 1600-0684
pISSN - 0047-2565
DOI - 10.1111/j.1600-0684.2004.00085.x
Subject(s) - genetic enhancement , vector (molecular biology) , viral vector , transgene , bone marrow , myelopoiesis , medicine , cytokine , immunology , biology , cancer research , gene , microbiology and biotechnology , haematopoiesis , recombinant dna , stem cell , biochemistry
Interleukin‐1 α (IL‐1 α ) is a multifunctional cytokine that stimulates myelopoiesis in macaque. However, daily systemic injections of IL‐1 α are associated with severe side effects. We therefore investigated the feasibility of a gene therapy strategy aimed at increasing the IL‐1 α local production in bone marrow with limited release of the vector into the blood circulation. Intra‐medullar administration of adenoviral vector containing human IL‐1 α (huIL‐1 α ) gene resulted in enhanced neutrophil, monocyte and platelet counts during the two first weeks after injection. The DNA vector, the transgene expression and the huIL‐1 α production was detected in treated bone marrow without significant detection of huIL‐1 α in the peripheral blood. Associated with huIL‐1 α production, we observed concomitant plasma C reactive protein and IL‐1Ra peaks in the acellular fraction of treated bone marrow at days 3 and 7. No abnormal clinical side effects were observed in any of the animals following the adenoviral vector injection.