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Abstract
Respirable antisense oligonucleotides (rAsONs) targeting discordantly expressed mediators of inflammation and/or bronchoconstriction and delivered to the lung via inhalation represent a new class of epigenetic-based therapeutics for asthma and other pulmonary diseases. The properties of these agents (solubility, chemical stability, rapid design based on primary DNA sequence information) combine synergistically with characteristics of the lung (non-invasive route of administration directly to the target organ, presence of uptake-modifying surfactant) to enhance the therapeutic potential of these oligonucleotide-based drugs. Their potential is further increased by the possibility of engineering antisense oligonucleotides whose effects are limited to the lung, reducing or avoiding the possibility of systemic toxicity.