Augmentation of Blood Platelet Levels by Intratracheal Administration of an Adenovirus Vector Encoding Human Thrombopoietin cDNA

Salvatore J. Cannizzo, Beat M. Frey, Shahin Raffi, Malcolm A.S. Moore, Dan Eaton, Motoyoshi Suzuki, Ravi Singh, Charles A. Mack, Ronald G. Crystal

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18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)570-573
Number of pages4
JournalNature Biotechnology
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 1997

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Keywords

  • Adenovirus
  • Gene therapy
  • Lung epithelium
  • Thrombopoietin

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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