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. 2007 May 1;9(4):840–853. doi: 10.1111/j.1582-4934.2005.tb00383.x

Antisense‐ and RNA interference‐based therapeutic strategies in allergy

Florin‐Dan Popescu 1,✉
PMCID: PMC6740309  PMID: 16364194

Abstract

Modern therapeutic methods for manipulation of gene expression in allergic diseases have been receiving increased attention in the emerging era of functional genomics. With the growing application of gene silencing technologies, pharmacological modulation of translation represents a great advance in molecular therapy for allergy. Several strategies for sequence‐specific post‐transcriptional inhibition of gene expression can be distinguished: antisense oligonucleotides (AS‐ONs), ribozymes (RZs), DNA enzymes (DNAzymes), and RNA interference (RNAi) triggered by small interfering RNAs (siRNAs). Potential anti‐mRNA drugs in asthma and other allergic disorders may be targeted to cell surface receptors (adenosine A1 receptor, high‐affinity receptor Fc‐RI‐α, cytokine receptors), adhesion molecules and ligands (ICAM‐1, VLA‐4), ion channels (calcium‐dependent chloride channel‐1), cytokines and related factors (IL‐4, IL‐5, IL‐13, SCF, TNF‐α, TGF‐β1), intracellular signal transduction molecules, such as tyrosine‐protein kinases (Syk, Lyn, Btk), serine/threonine‐protein kinases (p38 α MAP kinase, Raf‐1), non‐kinase signaling proteins (RasGRP4), and transcription factors involved in Th2 differentiation and allergic inflammation (STAT‐6, GATA‐3, NF‐kB). The challenge to scientists is to determine which of the candidate targets warrants investment of time and resources. New‐generation respirable AS‐ONs, external guide sequence ribozymes, and RNA interference‐based therapies have the potential to satisfy unmet needs in allergy treatment, acting at a more proximal level to a key etiopathogenetic molecular process, represented by abnormal expression of genes. Moreover, antisense and siRNA technologies imply a more rational design of new drugs for allergy.

Keywords: allergy, antisense oligonucleotides, ribozymes, DNAzymes, RNA interference, small interfering RNAs

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