Augmentation of blood platelet levels by intratracheal administration of an adenovirus vector encoding human thrombopoietin cDNA.
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.
Cannizzo
S J
SJ
Division of Pulmonary and Critical Care Medicine, New York Hospital-Cornell Medical Center, New York, USA.
Frey
B M
BM
Raffi
S
S
Moore
M A
MA
Eaton
D
D
Suzuki
M
M
Singh
R
R
Mack
C A
CA
Crystal
R G
RG
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*
D018076:DNA, Complementary; D011994:Recombinant Proteins; D013926:Thrombopoietin