Abstract
With the rapid revolution in RNA/DNA sequencing technologies, it is evident that mammalian genomes express tens of thousands of long noncoding RNAs (lncRNAs). Since a large majority of lncRNAs have been functionally implicated in cancer development and progression, there is an increasing appreciation for the use of antisense oligonucleotide (ASO)-based therapies targeting lncRNAs in several cancers. Despite their great potential in therapeutic applications, their use is still limited due to cellular toxicity and shortcomings in achieving required stability in biological fluids and tissue uptake. To overcome these limitations, major changes in ASO chemistry have been introduced to generate second and third generation ASOs, including locked nucleic acids (LNA) technology. Here we describe two different LNA-ASO delivery approaches, a peritumoral administration and a systemic delivery in xenograft models of lung adenocarcinoma, that significantly reduced tumor growth without inducing toxicity.
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Acknowledgments
This work was supported by the grants from Knut and Alice Wallenberg Foundation [KAW2014.0057], Swedish Foundation for Strategic Research [RB13-0204], Swedish Cancer Research foundation [Cancerfonden: Kontrakt no. CAN2018/591], Swedish Research Council [2017-02834], Barncancerfonden [PR2018-0090], Ingabritt Och Arne Lundbergs forskningsstiftelse, and LUA/ALF (to C.K.).
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Statello, L., Ali, M.M., Kanduri, C. (2021). In Vivo Administration of Therapeutic Antisense Oligonucleotides. In: Cao, H. (eds) Functional Analysis of Long Non-Coding RNAs. Methods in Molecular Biology, vol 2254. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1158-6_17
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DOI: https://doi.org/10.1007/978-1-0716-1158-6_17
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-1157-9
Online ISBN: 978-1-0716-1158-6
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