An RNA external guide sequence ribozyme targeting human interleukin-4 receptor alpha mRNA

International Immunopharmacology
D H DreyfusRamsay Fuleihan

Abstract

RNA oligonucleotides termed External Guide Sequence (EGS) and RNAi have been described that target specific gene expression by site-specific cleavage of mRNA. EGS serve as an RNA catalyst or ribozyme by directing bound mRNA to the ubiquitous cellular enzyme RNAse P. We describe an EGS targeting human interleukin (IL)-4 receptor alpha mRNA, an important cytokine receptor in the pathogenesis of asthma and allergic disease expressed in pulmonary tissues. This EGS was designed to explore pulmonary delivery of catalytic RNA oligonucleotides as a novel therapy in asthma and other atopic diseases. Inhaled DNA oligonucleotides termed Respirable Antisense OligoNucleotide Sequences (RASONS) are selectively internalized in lung tissues in a complex with endogenous lipid surfactants present in normal lung and can alter pulmonary gene expression. Potential applications of inhaled RNA oligonucleotides in therapy of pulmonary and related systemic diseases are discussed.

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Citations

Dec 15, 2006·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·David H Dreyfus
Oct 13, 2009·The Journal of Allergy and Clinical Immunology·Jeroen HolEdward E Nieuwenhuis
Dec 21, 2005·Journal of Cellular and Molecular Medicine·Florin-Dan Popescu
Apr 1, 2006·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Marina UlanovaA Dean Befus
Apr 14, 2015·Annals of the New York Academy of Sciences·Carol Davies-SalaMarcelo E Tolmasky

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