ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Regulation of activated microglia and macrophages by systemically administered DNA/RNA heteroduplex oligonucleotides.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- 5'tRNA-derived fragments modulate β-cell homeostasis and islet macrophage activation in type 2 diabetes.Nature communications · 2026Article
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Heteroduplex oligonucleotide technology boosts gene knockdown in cardiac and skeletal muscles.Nucleic acids research · 2026Article
- DNA/RNA Heteroduplex Oligonucleotide for Highly Efficient Gene Silencing.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Regulation of human microglial gene expression and function via RNAase-H active antisense oligonucleotides in vivo in Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Temporal changes of spinal microglia in murine models of neuropathic pain: a scoping review.Frontiers in immunology · 2024Article
- Nonviral delivery systems for antisense oligonucleotide therapeutics.Biomaterials research · 2022Review
- DNA/RNA heteroduplex oligonucleotides: An unanticipated twist in the delivery of ASOs.Molecular therapy. Nucleic acids · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microglial activation followed by recruitment of blood-borne macrophages into the central nervous system (CNS) aggravates neuroinflammation. Specifically, in multiple sclerosis (MS) as well as in experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, activated microglia and macrophages (Mg/Mφ) promote proinflammatory responses and expand demyelination in the CNS. However, a potent therapeutic approach through the systemic route for regulating their functions has not yet been developed. Here, we demonstrate that a systemically injected DNA/RNA heteroduplex oligonucleotide (HDO), composed of an antisense oligonucleotide (ASO) and its complementary RNA, conjugated to cholesterol (Chol-HDO) distributed more efficiently to demyelinating lesions of the spinal cord in EAE mice with significant gene silencing than the parent ASO. Importantly, systemic administration of Cd40-targeting Chol-HDO improved clinical signs of EAE with significant downregulation of Cd40 in Mg/Mφ. Furthermore, we successfully identify that macrophage scavenger receptor 1 (MSR1) is responsible for the uptake of Chol-HDO by Mg/Mφ of EAE mice. Overall, our findings demonstrate the therapeutic potency of systemically administered Chol-HDO to regulate activated Mg/Mφ in neuroinflammation.
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Registered trials
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