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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 22, 2025 |
| Title |
Lipid nanoparticles deliver DNA-encoded biologics and induce potent protective immunity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Lipid nanoparticles (LNPs) for mRNA delivery have advanced significantly, but LNP-mediated DNA delivery still faces clinical challenges. This study compared various LNP formulations for delivering DNA-encoded biologics, assessing their expression efficacy and the protective immunity generated by LNP-encapsulated DNA in different models. The LNP formulation used in Moderna’s Spikevax mRNA vaccine (LNP-M) demonstrated a stable nanoparticle structure, high expression efficiency, and low toxicity. Notably, a DNA vaccine encoding the spike protein, delivered via LNP-M, induced stronger antigen-specific antibody and T cell immune responses compared to electroporation. Single-cell RNA sequencing (scRNA-seq) analysis revealed that the LNP-M/pSpike vaccine enhanced CD80 activation signaling in CD8+ T cells, NK cells, macrophages, and DCs, while reducing the immunosuppressive signals. The enrichment of TCR and BCR by LNP-M/pSpike suggested an increase in immune response specificity and diversity. Additionally, LNP-M effectively delivered DNA-encoded antigens, such as mouse PD-L1 and p53R172H, or monoclonal antibodies targeting mouse PD-1 and human p53R282W. This approach inhibited tumor growth or metastasis in several mouse models. The long-term anti-tumor effects of LNP-M-delivered anti-p53R282W antibody relied on memory CD8+ T cell responses and enhanced MHC-I signaling from APCs to CD8+ T cells. These results highlight LNP-M as a promising and effective platform for delivering DNA-based vaccines and cancer immunotherapies.
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| Overall design |
CD45+ cells were isolated from spleens of mice immunized with LNP-M/Ctrl, LNP-M/mRNA-Spike, EP/pSpike, or LNP-M/pSpike). These cells were then subjected to single-cell RNA sequencing (scRNA-seq) to investigate the changes in immune cells within the spleens. Immune and non-immune cells were isolated from tumors of mice treated with LNP-M/pEL285K-mAb or LNP-M/Ctrl. The isolated cells were performed to the scRNA-seq to investigate the differences in tumor-infiltrating T cells within the tumors.
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| Contributor(s) |
Chai D, Wang J |
| Citation(s) |
39806486 |
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| Submission date |
Jul 22, 2024 |
| Last update date |
Jan 23, 2025 |
| Contact name |
Dafei Chai |
| E-mail(s) |
chaidafei8@gmail.com
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| Organization name |
Baylor College of Medicine
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| Street address |
Alkek Building One Baylor Plaza
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| City |
Houston |
| State/province |
Texas |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (20)
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| GSM8412800 |
LNP-M/pSpike, scRNA-seq (Spleen) |
| GSM8412801 |
LNP-M/Ctrl, scRNA-seq-TCR (Spleen) |
| GSM8412802 |
LNP-M/mRNA-Spike, scRNA-seq-TCR (Spleen) |
| GSM8412803 |
EP/pSpike, scRNA-seq-TCR (Spleen) |
| GSM8412804 |
LNP-M/pSpike, scRNA-seq-TCR (Spleen) |
| GSM8412805 |
LNP-M/Ctrl, scRNA-seq-BCR (Spleen) |
| GSM8412806 |
LNP-M/mRNA-Spike, scRNA-seq-BCR (Spleen) |
| GSM8412807 |
EP/pSpike, scRNA-seq-BCR (Spleen) |
| GSM8412808 |
LNP-M/pSpike, scRNA-seq-BCR (Spleen) |
| GSM8412809 |
LNP-M/Ctrl1, scRNA-seq (Tumor) |
| GSM8412810 |
LNP-M/Ctrl2, scRNA-seq (Tumor) |
| GSM8412811 |
LNP-M/pR282W-mAb1, scRNA-seq (Tumor) |
| GSM8412812 |
LNP-M/pR282W-mAb2, scRNA-seq (Tumor) |
| GSM8412813 |
LNP-M/Ctrl1, scRNA-seq-TCR (Tumor) |
| GSM8412814 |
LNP-M/Ctrl2, scRNA-seq-TCR (Tumor) |
| GSM8412815 |
LNP-M/pR282W-mAb1, scRNA-seq-TCR (Tumor) |
| GSM8412816 |
LNP-M/pR282W-mAb2, scRNA-seq-TCR (Tumor) |
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| Relations |
| BioProject |
PRJNA1138765 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE272803_RAW.tar |
506.5 Mb |
(http)(custom) |
TAR (of CSV, TAR) |
SRA Run Selector |
| Raw data are available in SRA |
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