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A Tetrahedral Framework DNA-Based Bioswitchable miR-150 Delivery System for Sepsis
Yutian He1, Zhiqiang Liu1, Songhang Li1
1State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
Abstract:
Sepsis is a disease with high morbidity and mortality, for which effective treatments are lacking. In recent years, microRNAs (miRs) have been shown to regulate numerous biological processes and can function as therapeutic options for various diseases. However, the poor stability and cell entry properties of miRs have greatly limited their clinical application. In this study, we developed a tetrahedral framework nucleic acid (tFNA)-based bioswitchable miR delivery system (BiRDS) to deliver miR-150 for the treatment of sepsis. BiRDS showed anti-inflammatory effects both in vitro and in vivo by regulating the NF-κB and Notch1 pathways. Therefore, this system holds promise as an ideal candidate for tackling systemic inflammation and multiorgan dysfunction in septic patients in the future.
Insights
Researchers developed a novel bioswitchable microRNA (miR) delivery system for sepsis treatment. This system effectively delivered miR-150, reducing inflammation and showing promise for treating sepsis complications.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Immunology
Background:
- Sepsis presents significant morbidity and mortality with limited effective treatments.
- MicroRNAs (miRs) regulate biological processes but face challenges in stability and cellular delivery for therapeutic use.
Purpose of the Study:
- To develop and evaluate a novel tetrahedral framework nucleic acid (tFNA)-based bioswitchable miR delivery system (BiRDS) for sepsis treatment.
- To assess the therapeutic efficacy of BiRDS delivering miR-150 in preclinical models of sepsis.
Main Methods:
- Development of a tFNA-based bioswitchable miR delivery system (BiRDS).
- In vitro and in vivo evaluation of BiRDS for miR-150 delivery in sepsis models.
- Analysis of the regulation of NF-κB and Notch1 pathways by BiRDS.
Main Results:
- BiRDS demonstrated effective delivery of miR-150 for sepsis treatment.
- The system exhibited significant anti-inflammatory effects both in vitro and in vivo.
- BiRDS modulated the NF-κB and Notch1 signaling pathways.
Conclusions:
- The BiRDS system holds promise as an effective therapeutic strategy for sepsis.
- This novel delivery system addresses limitations of miR stability and cell entry.
- BiRDS offers potential for managing systemic inflammation and multiorgan dysfunction in sepsis.
