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

David H. Dreyfus*, Agniesczka Matczuk, Ramsay Fuleihan

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

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 α 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.

Original languageEnglish (US)
Pages (from-to)1015-1027
Number of pages13
JournalInternational Immunopharmacology
Volume4
Issue number8
DOIs
Publication statusPublished - Aug 1 2004

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Keywords

  • Antisense DNA
  • Catalytic RNA
  • EGS
  • Human interleukin-4 receptor α mRNA
  • RASON
  • RNAi
  • RNAse P
  • Ribozyme

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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