Oligonucleotide therapies for the lung: ready to return to the clinic?

Kumar, Manish and Moschos, Sterghios (2017) Oligonucleotide therapies for the lung: ready to return to the clinic? Molecular Therapy, 25 (12). pp. 2604-2606. ISSN 1525-0016

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Official URL: https://doi.org/10.1016/j.ymthe.2017.11.002


The most promising targets for treating lung diseases are often intracellular molecules recalcitrant to conventional pharmacotherapy. In this respect, antisense oligonucleotides (ASO) would be valuable tools to treat airways disease, as the plurality of their potential mechanisms of action is well-established, their efficiency has been extensively validated in-vitro, and their potential clinical value has been demonstrated with numerous regulatory approvals.

Yet in spite of high confidence in the treatment rationale and mechanism of action, it appears that oligonucleotides delivered topically to the lung either rapidly access circulation via epithelial transcytosis or are removed by alveolar macrophages, exerting minimal if any action in the cytosol of cells relevant to lung disease. Moreover, use of cell penetrating peptides, liposomes or nanoparticle delivery systems has not so far been shown to eliminate circulatory clearance, may activate immune responses, or drive macrophage phenotypic changes that, together or in isolation, may present risks to patients.

Item Type: Article
Subjects: A100 Pre-clinical Medicine
A300 Clinical Medicine
B200 Pharmacology, Toxicology and Pharmacy
C400 Genetics
C700 Molecular Biology, Biophysics and Biochemistry
F100 Chemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Sterghios Moschos
Date Deposited: 15 Nov 2017 11:55
Last Modified: 11 Oct 2019 18:30
URI: http://nrl.northumbria.ac.uk/id/eprint/32527

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