title: Augmentation of blood platelet levels by intratracheal administration of an adenovirus vector encoding human thrombopoietin cDNA.
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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, New York Hospital-Cornell Medical Center, New York, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Cannizzo
authors.forename: B M
authors.initials: BM
authors.lastname: Frey
authors.forename: S
authors.initials: S
authors.lastname: Raffi
authors.forename: M A
authors.initials: MA
authors.lastname: Moore
authors.forename: D
authors.initials: D
authors.lastname: Eaton
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.forename: C A
authors.initials: CA
authors.lastname: Mack
authors.forename: R G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001854:Bone Marrow Cells; D002460:Cell Line; D003587:Cytomegalovirus; D018076:DNA, Complementary; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D016254:Mutagenesis, Insertional; D010976:Platelet Count; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000097:blood; D013154:Spleen / Q000166:cytology; D013926:Thrombopoietin / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D011994:Recombinant Proteins; D013926:Thrombopoietin