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Long Noncoding RNAs as Therapeutic Targets

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Long Noncoding RNA

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1363))

Abstract

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of cellular functions including maintenance of cellular homeostasis as well as the onset and progression of disease. LncRNAs often exhibit cell-, tissue-, and disease-specific expression patterns, making them desirable therapeutic targets. LncRNAs are commonly targeted using oligonucleotide therapeutics, and advances in oligonucleotide chemistry including C2 ribose sugar modifications such as 2′-fluoro, 2′-O-methyl, and 2-O-methoxyethyl modifications; 2′4′-constrained nucleotides such as locked nucleic acids and constrained 2′-O-ethyl (cEt) nucleotides; and phosphorothioate bonds have dramatically improved efficacy of oligonucleotide therapies. Novel delivery platforms such as viral vectors and nanoparticles have also improved pharmacokinetic properties of oligonucleotides targeting lncRNAs. Accumulating pre-clinical studies have utilized these strategies to therapeutically target lncRNAs and alter progression of many different disease states including Snhg12 and Chast in cardiovascular disease, Mirt2 and HOTTIP in sepsis and autoimmune disease, and Malat1 and HOXB-AS3 in cancer. Emerging oligonucleotide conjugation methods including the use of peptide nucleic acids hold promise to facilitate targeting to specific tissue types. Here, we review recent advances in lncRNA therapeutics and provide examples of how lncRNAs have been successfully targeted in pre-clinical models of disease. Finally, we detail remaining challenges facing the lncRNA field and how advances in delivery platforms and oligonucleotide chemistry might help overcome these barriers to catalyze the translation of pre-clinical studies to successful pharmaceutical development.

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Authors and Affiliations

  1. Department of Medicine, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Jacob B. Pierce, Haoyang Zhou, Viorel Simion & Mark W. Feinberg

  2. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Jacob B. Pierce

  3. Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China

    Haoyang Zhou

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  1. Jacob B. Pierce
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  2. Haoyang Zhou
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  3. Viorel Simion
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  4. Mark W. Feinberg
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Correspondence to Mark W. Feinberg .

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Editors and Affiliations

  1. Molecular Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA, USA

    Susan Carpenter

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Pierce, J.B., Zhou, H., Simion, V., Feinberg, M.W. (2022). Long Noncoding RNAs as Therapeutic Targets. In: Carpenter, S. (eds) Long Noncoding RNA. Advances in Experimental Medicine and Biology, vol 1363. Springer, Cham. https://doi.org/10.1007/978-3-030-92034-0_9

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