An RNA external guide sequence ribozyme targeting human interleukin-4 receptor alpha mRNA.
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.
Dreyfus
David H
DH
Department of Pediatrics, Yale School of Medicine, 488 Norton Parkway, New Haven, CT 06511, USA. dhdreyfus@pol.net
Matczuk
Agniesczka
A
Fuleihan
Ramsay
R
D000280:Administration, Inhalation; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D016373:DNA, Antisense / Q000008:administration & dosage*; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009690:Nucleic Acid Conformation; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D016337:RNA, Catalytic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D019948:Receptors, Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D043262:Ribonuclease P / Q000378:metabolism
D016373:DNA, Antisense; D018793:Interleukin-13; D021122:Protein Subunits; D016337:RNA, Catalytic; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D043262:Ribonuclease P