Virus Dataset Detail

> Detail information for each sample

Dataset Information
Accession GSE262515
Status 2024/4/2
Title Optimized RNA Interference Therapeutics Combined with Interleukin-2 mRNA for Treating Hepatitis B Virus Infection
Organism Homo sapiens;Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary BACKGROUND & AIMS: This study aimed to develop a pan-genotypic and multifunctional small interfering RNA (siRNA) against hepatitis B virus (HBV) with an efficient delivery system for treating chronic hepatitis B (CHB), and explore combined RNA interference (RNAi) and immune modulatory modalities for better viral control. METHODS: Twenty synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and evaluated. The lipid nanoparticle (LNP) formulation was optimized by adopting HO-PEG2000-DMG lipid and modifying the molar ratio of traditional polyethylene glycol (PEG) lipid in LNP prescriptions. The efficacy and safety of this formulation in delivering siHBV (tLNP/siHBV) along with the mouse IL-2 (mIL-2) mRNA (tLNP/siHBVIL2) were evaluated in the rAAV-HBV1.3 mouse model. RESULTS: A siRNA combination (terms “siHBV”) with a genotypic coverage of 98.55% was selected, chemically modified, and encapsulated within an optimized LNP (tLNP) of high efficacy and security to fabricate a therapeutic formulation for CHB. The results revealed that tLNP/siHBV significantly reduced the expression of viral antigens and DNA (up to 3log10 reduction) in dose- and time-dependent manners at single-dose or multi-dose frequencies, with satisfactory safety profiles. Further studies showed that tLNP/siHBVIL2 enables additive antigenic and immune control of the virus, via introducing potent HBsAg clearance through RNAi and triggering strong HBV-specific CD4+ and CD8+ T cell responses by expressed mIL-2 protein. CONCLUSIONS: By adopting tLNP as nucleic acid nanocarriers, the co-delivery of siHBV and mIL-2 mRNA enables synergistic antigenic and immune control of HBV, thus offering a promising translational therapeutic strategy for treating CHB.
Samples
GSM ID Sample info Characteristics Description
GSM8170783 HepG2-Mock, replicate1 tissue:cell line; cell line:Hepatocellular carcinoma; cell type:HepG2; genotype:WT; treatment:Mock -
GSM8170784 HepG2-Mock, replicate2 tissue:cell line; cell line:Hepatocellular carcinoma; cell type:HepG2; genotype:WT; treatment:Mock -
GSM8170785 HepG2-Mock, replicate3 tissue:cell line; cell line:Hepatocellular carcinoma; cell type:HepG2; genotype:WT; treatment:Mock -
GSM8170786 HepG2-tLNP/siNC, replicate1 tissue:cell line; cell line:Hepatocellular carcinoma; cell type:HepG2; genotype:WT; treatment:tLNP/siNC, 50nM -
GSM8170787 HepG2-tLNP/siNC, replicate2 tissue:cell line; cell line:Hepatocellular carcinoma; cell type:HepG2; genotype:WT; treatment:tLNP/siNC, 50nM -
GSM8170788 HepG2-tLNP/siNC, replicate3 tissue:cell line; cell line:Hepatocellular carcinoma; cell type:HepG2; genotype:WT; treatment:tLNP/siNC, 50nM -
GSM8170789 HepG2-tLNP/siHBV, replicate1 tissue:cell line; cell line:Hepatocellular carcinoma; cell type:HepG2; genotype:WT; treatment:tLNP/siHBV, 50nM -
GSM8170790 HepG2-tLNP/siHBV, replicate2 tissue:cell line; cell line:Hepatocellular carcinoma; cell type:HepG2; genotype:WT; treatment:tLNP/siHBV, 50nM -
GSM8170791 HepG2-tLNP/siHBV, replicate3 tissue:cell line; cell line:Hepatocellular carcinoma; cell type:HepG2; genotype:WT; treatment:tLNP/siHBV, 50nM -
GSM8170792 mouse-PBS, replicate1 tissue:tissue; cell line:liver; cell type:liver; genotype:C57BL/6; treatment:PBS -
GSM8170793 mouse-PBS, replicate2 tissue:tissue; cell line:liver; cell type:liver; genotype:C57BL/6; treatment:PBS -
GSM8170794 mouse-PBS, replicate3 tissue:tissue; cell line:liver; cell type:liver; genotype:C57BL/6; treatment:PBS -
GSM8170795 mouse-siNC-1mg/kg, replicate1 tissue:tissue; cell line:liver; cell type:liver; genotype:C57BL/6; treatment:tLNP/siNC, 1mg/kg -
GSM8170796 mouse-siNC-1mg/kg, replicate2 tissue:tissue; cell line:liver; cell type:liver; genotype:C57BL/6; treatment:tLNP/siNC, 1mg/kg -
GSM8170797 mouse-siNC-1mg/kg, replicate3 tissue:tissue; cell line:liver; cell type:liver; genotype:C57BL/6; treatment:tLNP/siNC, 1mg/kg -
GSM8170798 mouse-siHBV-1mg/kg, replicate1 tissue:tissue; cell line:liver; cell type:liver; genotype:C57BL/6; treatment:tLNP/siHBV, 1mg/kg -
GSM8170799 mouse-siHBV-1mg/kg, replicate2 tissue:tissue; cell line:liver; cell type:liver; genotype:C57BL/6; treatment:tLNP/siHBV, 1mg/kg -
GSM8170800 mouse-siHBV-1mg/kg, replicate3 tissue:tissue; cell line:liver; cell type:liver; genotype:C57BL/6; treatment:tLNP/siHBV, 1mg/kg -
GSM8170801 mouse-siHBV-2.5mg/kg, replicate1 tissue:tissue; cell line:liver; cell type:liver; genotype:C57BL/6; treatment:tLNP/siHBV, 2.5mg/kg -
GSM8170802 mouse-siHBV-2.5mg/kg, replicate2 tissue:tissue; cell line:liver; cell type:liver; genotype:C57BL/6; treatment:tLNP/siHBV, 2.5mg/kg -
GSM8170803 mouse-siHBV-2.5mg/kg, replicate3 tissue:tissue; cell line:liver; cell type:liver; genotype:C57BL/6; treatment:tLNP/siHBV, 2.5mg/kg -
Platform GPL16791  GPL17021  : Illumina HiSeq 2500 (Homo sapiens);Illumina HiSeq 2500 (Mus musculus)
Literature 38902241  
Download Download xCell Data  Download Expression Analysis Data  
xCell Plot
* p<0.05 ** p<0.01