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Lipid nanoparticles deliver DNA-encoded biologics and induce potent protective immunity

ABSTRACT: Lipid nanoparticles deliver DNA-encoded biologics and induce potent protective immunity

PROVIDER: PRJNA1138765 | ENA |

REPOSITORIES: ENA

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Lipid nanoparticles deliver DNA-encoded biologics and induce potent protective immunity

Project description: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.

2025-01-22 | GSE272803 | GEO

Facile Osteoimmunomodulatory Nanoparticles Augment 3D-Printed Scaffold-Mediated Bone Regeneration

Project description:Regenerating critical-sized long bone defects poses substantial challenges due to limitations of autografts and processed allografts. Biomaterial scaffolds offer versatile alternatives, yet their effectiveness is often constrained by their limited innate osteoinductivity. While growth factors and cells can enhance osteoinduction, the inclusion of biologics in biomaterial scaffolds creates regulatory challenges for clinical translation. To address this, here we describe three-dimensional (3D) printed polycaprolactone (PCL) scaffolds for temporally controlled delivery of osteoimmunomodulatory amorphous calcium phosphate-chitosan nanoparticles (ACPC-NP). In vitro, the ACPC-NP exhibit concentration dependent effects on osteoblasts, monocytes, and osteoclasts. At increasing concentrations up to 500 μg/ml, these nanoparticles stimulate osteogenesis, modulate M2/M1 macrophage polarization, and inhibit osteoclast maturation and activity. Leveraging these concentration-dependent effects in vivo through temporally controlled release of ACPC-NP from 3D-printed PCL scaffolds, we observe the complete regeneration and the restoration of biomechanical strength of critically sized radial defects in rats. Such healing is absent in defects implanted with bare PCL scaffolds or those loaded with calcium-phosphate microparticles. The tunable osteoimmunomodulation by the NP underscore the translational potential of this technology to yield structurally sound and functionally robust bone regeneration outcomes.

2024-07-02 | GSE262295 | GEO

Nanoparticles

Project description:Dietary silver nanoparticles can disturb the gut microbiota in mice

| PRJEB14370 | ENA

Functional Characterization of a Potent and Novel BET Inhibitor BBC1115 Identified from DNA-encoded Small Molecule Library Screening

Project description:Functional Characterization of a Potent and Novel BET Inhibitor BBC1115 Identified from DNA-encoded Small Molecule Library Screening

| PRJNA817156 | ENA

Application of Carbon Nanoparticles in Laparoscopic Colorectal Surgery

Project description:The project aims to evaluate the safety, effectiveness, accuracy and economy efficiency of the application of carbon nanoparticles for tumor localization and lymph nodes mapping in the laparoscopic coloectal surgery.

| 2259563 | ecrin-mdr-crc

Profile of micro-RNA in ginger-derived nanoparticles

Project description:Comparative analysis of micro-RNA (miRNA) in ginger-derived nanoparticles and ginger donor tissue using next-generation sequencing (NGS). The ginger-derived nanoparticles were prepared by differential ultracentrifuges. We mapped about 30 to 50 million sequence reads to the plant miRNA database and identified total of 2228 miRNAs including 532 miRNAs higher in nanoparticles and 1,280 miRNAs higner in tissue.

2021-05-19 | GSE153126 | GEO

Gene expression analysis of EBV-encoded dUTPase in hDCs

Project description:Gene expression patterns provide insight into complex biological networks in which viruses and host cells interact. Dendritic cells are the most potent antigen presenting cells of the immune system and are crucial for the initiation of T-cell responses to viral pathogens. To better understand the biological effects of the EBV-encoded dUTPase on gene modulation in cells that play a central role in innate and adaptive immune responses, microarray gene expression profiling studies were performed in untreated or EBV-encoded dUTPase treated hDCs using the human genome U133 Plus 2.0 GeneChip. The results of this study identified over 800 differentially expressed genes between control and EBV-encoded dUTPase treated samples for each normalized data set using the criteria fold change >2 and p<0.05.

2014-12-31 | GSE46519 | GEO

Cell response to Au nanoparticles

Project description:Human skin fibroblast treated with Au nanoparticles induced gene expression changes Keywords: Time course and dose response

2008-01-20 | GSE6818 | GEO

Transcription profiling of tomato leaves treated with harpin, chitosan nanoparticles and harpin loaded chitosan nanoparticles against untreated controls

Project description:We studied the transcriptome changes in tomato against treatment with harpinPss, chitosan nanoparticles (CSNPs), and harpin loaded chitosan nanoparticles (H-CSNPs). We measured and compared the difference in transcript accumulation between treated- and control tomato leaves. Two independent experiments were performed at each time (24 h, 48 h and 72 h).

2018-06-30 | GSE100594 | GEO

Expression data from mouse liver tissue from SKH:QS mice treated with commercially available sunscreens containing ZnO or TiO2 nanoparticles, or no nanoparticles

Project description:ZnO and TiO2 nanoparticles can elicit a range of perturbed cell responses in vitro. Exposure to topically applied sunscreens containing ZnO or TiO2 particles may or may not elicit a biological effect in mice. We aimed to compare the biological responses of immune-competent hairless mice receiving topical applications of commercially available sunscreens with or without metal oxide nanoparticles, with the responses of mice receiving no sunscreen. Commercially available sunscreens containing ZnO nanoparticles, a mixture of TiO2 nanoparticles and organic UVR filters, or only organic UVR filters were applied to the backs of SKH:QS mice weekly over 36 weeks, with or without subsequent exposure to 29 kJ/m2 UVR. After 36 weeks and 30 treatments, mice were sacrificed and liver tissue was harvested for RNA isolation and whole genome transcriptional profiling, comparing the expression profiles of treated mice with untreated mice.

2016-07-26 | E-GEOD-84818 | biostudies-arrayexpress

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