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Is There a Role for Immunoregulatory and Antiviral Oligonucleotides Acting in the Extracellular Space? A Review and Hypothesis

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اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • Publisher Information:
      Stockholms universitet, Institutionen för molekylär biovetenskap, Wenner-Grens institut 2022
    • نبذة مختصرة :
      Here, we link approved and emerging nucleic acid-based therapies with the expanding universe of small non-coding RNAs (sncRNAs) and the innate immune responses that sense oligonucleotides taken up into endosomes. The Toll-like receptors (TLRs) 3, 7, 8, and 9 are located in endosomes and can detect nucleic acids taken up through endocytic routes. These receptors are key triggers in the defense against viruses and/or bacterial infections, yet they also constitute an Achilles heel towards the discrimination between self- and pathogenic nucleic acids. The compartmentalization of nucleic acids and the activity of nucleases are key components in avoiding autoimmune reactions against nucleic acids, but we still lack knowledge on the plethora of nucleic acids that might be released into the extracellular space upon infections, inflammation, and other stress responses involving increased cell death. We review recent findings that a set of single-stranded oligonucleotides (length of 25–40 nucleotides (nt)) can temporarily block ligands destined for endosomes expressing TLRs in human monocyte-derived dendritic cells. We discuss knowledge gaps and highlight the existence of a pool of RNA with an approximate length of 30–40 nt that may still have unappreciated regulatory functions in physiology and in the defense against viruses as gatekeepers of endosomal uptake through certain routes.
    • الموضوع:
      oligonucleotide; TLR; sncRNA; endocytosis; broad-spectrum; antiviral agent; nucleolin; virus entry; immunoregulation; RNA therapeutics; Cell and Molecular Biology; Cell- och molekylärbiologi; Article, review/survey; info:eu-repo/semantics/article; text
    • الرقم المعرف:
      10.3390.ijms232314593
    • Note:
      English
    • Other Numbers:
      UPE oai:DiVA.org:su-213809
      0000-0003-3259-634x
      0000-0001-6367-5951
      0000-0003-3964-9512
      doi:10.3390/ijms232314593
      PMID 36498932
      ISI:000897557700001
      Scopus 2-s2.0-85143745098
      1372247935
    • Contributing Source:
      UPPSALA UNIV LIBR
      From OAIster®, provided by the OCLC Cooperative.
    • الرقم المعرف:
      edsoai.on1372247935
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