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

Nature Biotechnology
S J CannizzoR G Crystal

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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Citations

Sep 30, 2000·Stem Cells·A L TaskinF Wendling
Aug 30, 2008·Science in China. Series C, Life Sciences·S ChongJ Xue
Oct 23, 2013·Current Hematologic Malignancy Reports·Niccolò BartalucciAlessandro M Vannucchi
Jun 15, 1999·Trends in Pharmacological Sciences·D L Ennist
Jun 20, 2006·Best Practice & Research. Clinical Haematology·Hedia ChagraouiWilliam Vainchenker
Feb 13, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·D WolfeJ C Glorioso
Dec 9, 2016·Human Gene Therapy·Dolan SondhiRonald G Crystal
Jul 30, 2005·Circulation Research·Hideki AmanoRonald G Crystal

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