HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/5/L1066    most recent 00067.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (25) Citing Articles via Google Scholar Google Scholar Articles by Massaro, D. Articles by Clerch, L. B. Search for Related Content PubMed PubMed Citation Articles by Massaro, D. Articles by Clerch, L. B.

INNOVATIVE METHODOLOGY

Noninvasive delivery of small inhibitory RNA and other reagents to pulmonary alveoli in mice

Lung Biology Laboratory, Departments of ¹Medicine and ²Pediatrics, Georgetown University School of Medicine, Washington, District of Columbia 20057-1481

Submitted 1 March 2004 ; accepted in final form 25 June 2004

A technically easy, noninvasive means of delivering molecules to alveoli, which act selectively or specifically in the lung, would be experimentally and therapeutically useful. As proof of principle, we took advantage of the spreading ability of pulmonary surface active material (InfaSurf), mixed it with elastase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) small inhibitory RNA (siRNA), or all-trans retinoic acid (ATRA), and instilled microliter amounts of the mixture into the nose of lightly anesthetized mice. One instillation of elastase caused diffuse alveolar destruction (emphysema) demonstrating widespread alveolar delivery. A single nasal instillation of GAPDH siRNA, compared with scrambled GAPDH siRNA, lowered GAPDH protein in lung, heart, and kidney by 50–70% 1 and 7 days later. To test the possibility of lung-specific delivery of a potentially therapeutic drug, we administered ATRA and monitored its effect on expression of cellular retinol binding protein (CRBP)-1 mRNA, whose translation product is a key molecule in retinoid metabolism. Given intranasally, ATRA elevated CRBP-1 mRNA 4.3-fold in a lung-specific manner. The same dose and dose schedule of ATRA given intraperitoneally increased CRBP-1 mRNA only 1.8-fold in lung; intraperitoneally administered ATRA elevated expression of CRBP-1 mRNA 1.7-fold or more in brain cortex, cerebellum, and testes, thereby increasing the risk of untoward effects. This simple noninvasive technique allows regulation of specific proteins in the lung and lung-specific delivery of reagents of experimental and potentially therapeutic importance.

bronchopulmonary dysplasia; emphysema; brain; kidney; retinoic acid

This article has been cited by other articles:

				N. Matsuda, Y. Takano, S.-i. Kageyama, N. Hatakeyama, K. Shakunaga, I. Kitajima, M. Yamazaki, and Y. Hattori Silencing of caspase-8 and caspase-3 by RNA interference prevents vascular endothelial cell injury in mice with endotoxic shock Cardiovasc Res, October 1, 2007; 76(1): 132 - 140. [Abstract] [Full Text] [PDF]

				T. Li and H. G. Folkesson RNA interference for {alpha}-ENaC inhibits rat lung fluid absorption in vivo Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L649 - L660. [Abstract] [Full Text] [PDF]