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Selecting Therapeutic Antisense Oligonucleotides with Gene Targeting and TLR8 Potentiating Bifunctionality

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Inflammation and Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2691))

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Abstract

A growing body of preclinical evidence has led to the hypothesis that human Toll-like receptor 8 (hTLR8) activation in the tumor microenvironment (TME) could have potent anticancer effects through its action on monocytes, myeloid dendritic cells (mDCs), and natural killer (NK) cells. This has motivated the initiation of several clinical trials for chemical hTLR8 agonists in a variety of cancers. Concurrently, a growing number of synthetic antisense oligonucleotides (ASOs) are being developed as cancer therapeutics. We have recently reported that 2′-O-methyl (2′OMe)-modified ASOs can potentiate sensing of hTLR8 chemical agonists in a sequence-dependent manner. This suggests that select gene-targeting ASOs with anticancer activity may synergize with low-dose hTLR8 agonists in the TME. Here, we provide a detailed protocol to rapidly screen and identify such synthetic bifunctional oligonucleotides with synergistic activity on hTLR8 sensing.

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Acknowledgements

We thank M. Speir for editorial assistance. This work was supported by funding from the Australian National Health and Medical Research Council (2020565 to MG) and the Victorian Government’s Operational Infrastructure Support Program.

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Authors and Affiliations

  1. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia

    Sunil Sapkota & Michael P. Gantier

  2. Department of Molecular and Translational Science, Monash University, Clayton, VIC, Australia

    Sunil Sapkota & Michael P. Gantier

Authors
  1. Sunil Sapkota
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  2. Michael P. Gantier
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Corresponding author

Correspondence to Michael P. Gantier .

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Editors and Affiliations

  1. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia

    Brendan J. Jenkins

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© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Sapkota, S., Gantier, M.P. (2023). Selecting Therapeutic Antisense Oligonucleotides with Gene Targeting and TLR8 Potentiating Bifunctionality. In: Jenkins, B.J. (eds) Inflammation and Cancer. Methods in Molecular Biology, vol 2691. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3331-1_17

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  • DOI: https://doi.org/10.1007/978-1-0716-3331-1_17

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3330-4

  • Online ISBN: 978-1-0716-3331-1

  • eBook Packages: Springer Protocols

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