Treating Autoimmune Diseases by Targeting IL-23 with Gene-Silencing Pyrrole–Imidazole Polyamide

He, Xiaozhen; Liu, Ruiling; Fan, Tingting; Huang, Xiaowen; Wu, Chunhui; Wu, Songhua; Wang, Ting; Ruan, Qingguo

doi:10.4049/jimmunol.1901215

Cited by 4 publications

(2 citation statements)

References 39 publications

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“…Recently, He et al. (2020) 94 designed a PIP targeting IL‐23p19 subunit promoter specific to the transcription factor c‐Rel binding site (Figure 9). This PIP efficiently entered the nucleus of dendritic cells and macrophages to inhibit the binding of c‐Rel to the IL‐23p19 promoter in vivo by suppressing IL‐23 expression.…”

Section: Designing Pips To Modulate Diverse Transcriptional Targetsmentioning

confidence: 99%

Nucleic acid‐based small molecules as targeted transcription therapeutics for immunoregulation

Bai,

Ziadlou,

Vaijayanthi

et al. 2023

Allergy

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Transcription therapy is an emerging approach that centers on identifying the factors associated with the malfunctioning gene transcription machinery that causes diseases and controlling them with designer agents. Until now, the primary research focus in therapeutic gene modulation has been on small‐molecule drugs that target epigenetic enzymes and critical signaling pathways. However, nucleic acid‐based small molecules have gained popularity in recent years for their amenability to be pre‐designed and realize operative control over the dynamic transcription machinery that governs how the immune system responds to diseases. Pyrrole–imidazole polyamides (PIPs) are well‐established DNA‐based small‐molecule gene regulators that overcome the limitations of their conventional counterparts owing to their sequence‐targeted specificity, versatile regulatory efficiency, and biocompatibility. Here, we emphasize the rational design of PIPs, their functional mechanisms, and their potential as targeted transcription therapeutics for disease treatment by regulating the immune response. Furthermore, we also discuss the challenges and foresight of this approach in personalized immunotherapy in precision medicine.

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Section: Designing Pips To Modulate Diverse Transcriptional Targetsmentioning

confidence: 99%

Nucleic acid‐based small molecules as targeted transcription therapeutics for immunoregulation

Bai,

Ziadlou,

Vaijayanthi

et al. 2023

Allergy

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“…It is approved for the treatment of psoriasis [67]. Another recent approach is a gene-silencing Py-Im polyamide that can enter the nucleus and compete with c-Rel for binding at the IL-23p19 promotor, therefore limiting IL-23 expression on DNA level [68]. However, application of previously admitted drugs is still limited to few diseases and further clinical studies to expand treatment options are essential.…”

Section: Treatments Targeting Il-23mentioning

confidence: 99%

Persistence, Pathogenicity and Plasticity: The Role of IL-23 in Th17 Fate

2022

Journal of Cellular Immunology

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For a long time Th1 cells were considered the key players in the induction of inflammation and progression of disease in autoimmune diseases. With the discovery of IL-17-producing CD4 + T cells (Th17) being abundant at inflammation sites, this soon changed. Investigating this new T helper subset, it became clear that in comparison to Th1 and Th2 cells, Th17 cells have an increased tendency to change their phenotype and therefore become either more pathogenic or immunoregulatory. This makes them an attractive target for therapeutic interventions. As plasticity of Th17 cells differs between different autoimmune diseases, understanding its drivers is complex. This review focusses on the role of plasticity within Th17 cells in induction, aggravation and resolution of disease and points out IL-23 as a potential key player in controlling Th17 fate. Finally, current treatments targeting IL-23 and Th17 plasticity are highlighted and an outlook on future therapeutics is given.

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Associations between IL-23R gene polymorphism (rs10889677 A/C) and ankylosing spondylitis and rheumatoid arthritis susceptibility: A meta-analysis with trial sequential analysis

Zhang

Shao

et al. 2022

Autoimmunity

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Treating Autoimmune Diseases by Targeting IL-23 with Gene-Silencing Pyrrole–Imidazole Polyamide

Cited by 4 publications

References 39 publications

Nucleic acid‐based small molecules as targeted transcription therapeutics for immunoregulation

Nucleic acid‐based small molecules as targeted transcription therapeutics for immunoregulation

Persistence, Pathogenicity and Plasticity: The Role of IL-23 in Th17 Fate

Associations between IL-23R gene polymorphism (rs10889677 A/C) and ankylosing spondylitis and rheumatoid arthritis susceptibility: A meta-analysis with trial sequential analysis

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