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Augmentation of blood platelet levels by intratracheal administration of an adenovirus vector encoding human thrombopoietin cDNA

Nature Biotechnology volume 15, pages 570–573 (1997)Cite this article

Abstract

This study was designed to evaluate the hypothesis that administration of a replication-deficient, recombinant adenovirus vector to the epithelial surface of the respiratory tract can be used to deliver a recombinant protein to the systemic circulation in sufficient quantities to evoke a systemic response appropriate to the recombinant protein. We administered AdCMV.TPO—an adenovirus vector containing an expression cassette coding for the human thrombopoietin (TPO) cDNA—to the respiratory epithelium of immunocompetent Balb/c mice. Over the following week, serum human TPO levels were elevated, platelet levels increased more than sixfold, and megakaryocytosis was evident in bone marrow. This strategy may be a useful approach to the nonparenteral administration of a variety of therapeutic recombinant proteins, such as those relevant to clotting, endocrine function, and bone-marrow function.

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Author notes

  1. Ronald G. Crystal: Corresponding author.

Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, The New York Hospital–Cornell Medical Center, New York, NY

    Salvatore J. Cannizzo, Motoyoshi Suzuki, Ravi Singh & Charles A. Mack

  2. James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York, NY

    Beat M. Frey & Malcolm A.S. Moore

  3. Division of Hematology-Oncology, The New York Hospital–Cornell Medical Center, New York, NY

    Shahin Raffi

  4. Genentech, Inc., Cardiovascular Research Department, South San Francisco, CA.

    Dan Eaton

Authors
  1. Salvatore J. Cannizzo
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  4. Malcolm A.S. Moore
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  9. Ronald G. Crystal
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Cannizzo, S., Frey, B., Raffi, S. et al. Augmentation of blood platelet levels by intratracheal administration of an adenovirus vector encoding human thrombopoietin cDNA. Nat Biotechnol 15, 570–573 (1997). https://doi.org/10.1038/nbt0697-570

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  • DOI: https://doi.org/10.1038/nbt0697-570

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