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editorial
. 2020 Aug 19;11(9):1659–1660. doi: 10.1021/acsmedchemlett.0c00421

RNA: Opening New Doors in Medicinal Chemistry

Amanda L Garner ✉, Stevan W Djuric
PMCID: PMC7488281  PMID: 32944131

Over the past few years, we have witnessed an explosion in new modalities in drug discovery. RNA, both as a drug and a drug target, has undergone a rebirth in this landscape. To celebrate this occasion in drug discovery, in 2021, we intend to publish a Special Issue, “RNA: Opening New Doors in Medicinal Chemistry.”

Although previously regarded as a simple intermediate between genes and proteins, the completion of the human genome project surprisingly revealed that the vast majority of our genome, over 98%, encodes for noncoding RNAs such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs).1 This has subsequently led to an RNA renaissance in biology and medicine, uncovering the fundamental roles that RNAs, and RNA biology more generally, play in the maintenance of human health and connection to disease. Aberrant regulation of noncoding RNAs has now been linked to nearly all human pathologies from neurodegenerative diseases to cancer and metabolic disorders.2−4 Targeting of coding RNAs, rather than the proteins in which they encode, has also emerged as a new therapeutic strategy for affecting the biology of as-yet undruggable protein targets.5 In addition to human RNAs, RNAs from other organisms, including bacterial RNAs6 and RNA viruses,7 are regarded as leading drug targets for the discovery of new infectious disease agents. Combined, the search for and development of RNA-targeted therapeutics has never been more pressing.

Yet, RNA structure–function and RNA biology are complex and often unexplored, underscoring a growing need for multifaceted approaches in RNA-targeted drug discovery.8−15 Thus, we are inviting scientists working in diverse areas of medicinal chemistry to contribute their research efforts and/or thoughts for this Special Issue so that they may be shared with our wide-ranging readership. We welcome content from the broad RNA community, including efforts in targeting RNA structures with small molecules, targeting RNA-binding proteins and RNA-modifying enzymes, the development of RNA-based biologic drugs, and methods development related to advancing the field of RNA-targeted therapeutics.

The Guest Editors, Amanda L. Garner (University of Michigan) and Stevan W. Djuric will be working together to publish this issue in mid-2021.

We encourage you to submit your manuscripts at https://acsparagonplus.acs.org by December 31, 2020. Please select “RNA: Opening New Doors in Medicinal Chemistry” from the special issue dropdown box in the ACS Paragon Plus submission system. We are seeking original manuscripts in the form of Letters, Notes and Technology Notes, as well as Viewpoints and Innovations. For more information about the journal scope and manuscript types, please review the Author Guidelines: https://pubsapp.acs.org/paragonplus/submission/amclct/smclct_authguide.pdf. All manuscripts will proceed through the standard ACS Med. Chem. Lett. rigorous review and editorial process.

We look forward to celebrating this new frontier in medicinal chemistry through this Special Issue.

Views expressed in this editorial are those of the authors and not necessarily the views of the ACS.

Notes

Views expressed in this editorial are those of the authors and not necessarily the views of the ACS.

References

  1. Djebali S.; Davis C. A.; Merkel A.; Dobin A.; Lassmann T.; Mortazavi A.; Tanzer A.; Lagarde J.; Lin W.; Schlesinger F.; Xue C.; Marinov G. K.; Khatun J.; Williams B. A.; Zaleski C.; Rozowsky J.; Roder M.; Kokocinski F.; Abdelhamid R. F.; Alioto T.; Antoshechkin I.; Baer M. T.; Bar N. S.; Batut P.; Bell K.; Bell I.; Chakrabortty S.; Chen X.; Chrast J.; Curado J.; Derrien T.; Drenkow J.; Dumais E.; Dumais J.; Duttagupta R.; Falconnet E.; Fastuca M.; Fejes-Toth K.; Ferreira P.; Foissac S.; Fullwood M. J.; Gao H.; Gonzalez D.; Gordon A.; Gunawardena H.; Howald C.; Jha S.; Johnson R.; Kapranov P.; King B.; Kingswood C.; Luo O. J.; Park E.; Persaud K.; Preall J. B.; Ribeca P.; Risk B.; Robyr D.; Sammeth M.; Schaffer L.; See L. H.; Shahab A.; Skancke J.; Suzuki A. M.; Takahashi H.; Tilgner H.; Trout D.; Walters N.; Wang H.; Wrobel J.; Yu Y.; Ruan X.; Hayashizaki Y.; Harrow J.; Gerstein M.; Hubbard T.; Reymond A.; Antonarakis S. E.; Hannon G.; Giddings M. C.; Ruan Y.; Wold B.; Carninci P.; Guigo R.; Gingeras T. R. Landscape of transcription in human cells. Nature 2012, 489, 101–108. 10.1038/nature11233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Rupaimoole R.; Slack F. J. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat. Rev. Drug Discovery 2017, 16, 203–221. 10.1038/nrd.2016.246. [DOI] [PubMed] [Google Scholar]
  3. Matsui M.; Corey D. R. Non-coding RNAs as drug targets. Nat. Rev. Drug Discovery 2017, 16, 167–179. 10.1038/nrd.2016.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bernat V.; Disney M. D. RNA structures as mediators of neurological diseases and as drug targets. Neuron 2015, 87, 28–46. 10.1016/j.neuron.2015.06.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Warner K. D.; Hajdin C. E.; Weeks K. M. Principles for targeting RNA with drug-like small molecules. Nat. Rev. Drug Discovery 2018, 17, 547–558. 10.1038/nrd.2018.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Howe J. A.; Wang H.; Fischmann T. O.; Balibar C. J.; Xiao L.; Galgoci A. M.; Malinverni J. C.; Mayhood T.; Villafania A.; Nahvi A.; Murgolo N.; Barbieri C. M.; Mann P. A.; Carr D.; Xia E.; Zuck P.; Riley D.; Painter R. E.; Walker S. S.; Sherborne B.; de Jesus R.; Pan W.; Plotkin M. A.; Wu J.; Rindgen D.; Cummings J.; Garlisi C. G.; Zhang R.; Sheth P. R.; Gill C. J.; Tang H.; Roemer T. Selective small-molecule inhibition of an RNA structural element. Nature 2015, 526, 672–677. 10.1038/nature15542. [DOI] [PubMed] [Google Scholar]
  7. Hermann T. Viral RNA targets and their small molecule ligands. Top. Med. Chem. 2017, 27, 111–134. 10.1007/7355_2016_20. [DOI] [Google Scholar]
  8. Ursu A.; Vezina-Dawod S.; Disney M. D. Methods to identify and optimize small molecules interacting with RNA (SMIRNAs). Drug Discovery Today 2019, 24, 2002–2016. 10.1016/j.drudis.2019.06.019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Costales M. G.; Childs-Disney J. L.; Haniff H. S.; Disney M. D. How we think about targeting RNA with small molecules. J. Med. Chem. 2020, 10.1021/acs.jmedchem.9b01927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Crooke S. T.; Witztum J. L.; Bennett C. F.; Baker B. F. RNA-targeted therapeutics. Cell Metab. 2018, 27, 714–739. 10.1016/j.cmet.2018.03.004. [DOI] [PubMed] [Google Scholar]
  11. Boriack-Sjodin P. A.; Ribich S.; Copeland R. A. RNA-modifying proteins as anticancer drug targets. Nat. Rev. Drug Discovery 2018, 17, 435–453. 10.1038/nrd.2018.71. [DOI] [PubMed] [Google Scholar]
  12. Wu P. Inhibition of RNA-binding proteins with small molecules. Nat. Rev. Chem. 2020, 10.1038/s41570-020-0201-4. [DOI] [PubMed] [Google Scholar]
  13. Boer R. E.; Torrey Z. R.; Schneekloth J. S. Jr. Chemical modulation of pre-mRNA splicing in mammalian systems. ACS Chem. Biol. 2020, 15, 808–818. 10.1021/acschembio.0c00001. [DOI] [PubMed] [Google Scholar]
  14. Stanton M. G.; Murphy-Benenato K. E. Messenger RNA as a novel therapeutic approach. Top. Med. Chem. 2017, 27, 237–253. 10.1007/7355_2016_30. [DOI] [Google Scholar]
  15. Wessels H.-H.; Mendez-Mancilla A.; Guo X.; Legut M.; Daniloski Z.; Sanjana N. E. Massively parallel Cas13 screens reveal principles for guide RNA design. Nat. Biotechnol. 2020, 38, 722–727. 10.1038/s41587-020-0456-9. [DOI] [PMC free article] [PubMed] [Google Scholar]

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