Lipid Nanoparticle-Mediated Delivery of Anti-miR-17 Family Oligonucleotide Suppresses Hepatocellular Carcinoma Growth
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA362544 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-06-01 | GSE93832 | GEO
Project description:We report the development of a new multiomic nanoparticle delivery system called Single cEll Nanoparticle Transcriptome-sequencing (SENT-seq), which quantifies how dozens of lipid nanoparticles (LNPs) deliver DNA barcodes and mRNA into cells, subsequent protein production, and the transcriptome, with single cell resolution. We show from the sequencing data that cell heterogeneity influences the efficiency with which LNPs deliver mRNA therapies, and identify cell subtypes that exhibit particularly high or low LNP uptake as well as genes associated with those subtypes. These data suggest that cell subsets have distinct responses to LNPs, and that these differential interactions can affect mRNA therapies.
2023-01-23 | GSE186395 | GEO
Project description:Apatite nanoparticle(sCA)-siTIMP1 delivery in NIH3T3
| PRJNA526507 | ENA
Project description:Antisense oligonucleotides (ASOs) are being actively investigated as potential therapeutics for a broad range of neurodegenerative diseases. While these small oligonucleotides have been effective in the clinic, many basic questions regarding ASO internalization, trafficking, and modes of enhancing delivery remain. To address these questions, we investigated how lipid nanoparticle (LNP) delivery affects ASO uptake and distribution in the brain. We show that ASOs are internalized and active in central nervous system (CNS) cell types both in vivo and in vitro. While differential cellular activity and polarization states do not affect ASO potency, encapsulating ASOs in LNPs increases ASO activity up to 100-fold in cultured CNS cells. This dramatic increase in efficacy is facilitated by the intracellular trafficking of ASOs away from lysosomes or enhanced ASO uptake, which is cell-type-specific. We assessed the translatability of these results by screening ASO-LNPs in vitro and intracerebroventricularly injecting top performing formulations in mice. ASO-LNP delivery induced a strong ASO-dependent microgliosis response in the brain revealing that LNP encapsulation cannot mask ASO-mediated toxicity. However, LNP-delivered ASOs did not downregulate mRNA levels in bulk tissue due to changes in ASO distribution. While ASOs distribute widely across the brain after bulk injection, ASO-LNPs are preferentially internalized by cells lining the blood vessels and ventricles. Consistent with our findings in cells, ASOs localize to the endolysosomal system following both ASO and ASO-LNP delivery in the brain as determined using immunoelectron microscopy. These data provide valuable insights into how LNPs regulate ASO uptake and distribution in the brain, and support further development of ASO-LNPs for treating CNS disorders.
2023-05-15 | GSE220777 | GEO
Project description:Nanoparticle stereochemistry-dependent endocytosis improves in vivo mRNA delivery
| PRJNA751588 | ENA
Project description:Gold nanoparticle (AuâNP) oligonucleotide complexes hold considerable promise as an approach for manipulating intracellular gene regulation. We show that the uptake and intracellular fate of AuâNP oligonucleotide complexes is associated with endocytosis and signal transduction. A transcriptomeâwide functional analysis of gene expression implicated multiple signaling pathways specific for AuâNP oligonucleotide complexes. In primary immune cells, the complexes trigger the expression of proâinflammatory nonâchemotactic cytokines rather than the many IFNâstimulated genes critical for induction of the immune response to a microbial challenge. Concordant with these changes, exposure to AuâNP oligonucleotide complexes is also accompanied by marked activation of immune cells. This distinct gene expression profile is not replicated in the lineageârestricted 293T cell line. These findings provide insight into the functional significance of the recruitment of AuâNP oligonucleotide complexes to endocytic structures and highlight the need to study the systems effects of nanomaterials in a biologically relevant model. We investigated the effect of AuâNP antisense EGFP oligonucleotide complexes on the transcriptome by expression profiling of 293T cells under four conditions and PBMCs under six conditions plus HIV infection with the Affymetrix U133 Plus 2.0 microarray. To control for experimental variability, three of the six PBMC conditions (24â and 48âhours after AuâNP oligonucleotide complex treatment, and the negative control) were assayed independently a second time (biological replicates) so that 13 microarrays were hybridized in total. A different batch of AuâNP oligonucleotide complexes was used in the generation of the four 293T and three replicate PBMC samples, and the microarrays for these samples were processed separately.
2010-04-06 | E-GEOD-20677 | biostudies-arrayexpress
Project description:Nanoparticles and nano delivery systems are continuously being refined and developed as means of treating numerous human diseases by site-specific, and target-oriented delivery of medicines. The nanoparticles can carry therapeutic cargo or be medicinal themselves by virtue of their constitutional structural components. Here we report the ability of synthetic N-acylethanolamides, linoleoylethanolamide (LEA) and oleoylethanolamide (OEA), with endocannabinoid-like activity, to form spherical colloidal nanoparticles that when conjugated with tissue specific homing molecules, can localise to specific areas of the body, and reduce inflammation. The opportunities to mediate pharmacological effects of endocannabinoids at targeted sites provides a novel drug delivery system with increased medicinal potential to treat many diseases in many areas of medicine.
2022-10-19 | GSE206164 | GEO
Project description:Silencing HoxA1 in vivo by intraductal delivery of nanoparticle-formulated siRNA reduced mammary tumor incidence by 75% , reduced cell proliferation, and prevented loss of ER and PR expression. 8 week wild type FVB mouse whole mammary gland and 8week to 20 week transgenic FVB C3(1)-SV40Tag mouse whole mammary gland
2013-12-31 | E-GEOD-50813 | biostudies-arrayexpress
Project description:Expression profiling of sCA-siRNA delivery in NIH3T3 cells (siControl vs. siTIMP1) Goal was to determine the off target effects of sCA-siTIMP1 in NIH3T3 cells.
2020-08-27 | GSE128124 | GEO
Project description:RNA interference (RNAi) has immense potential to modulate cell functions. However, effective delivery of siRNA while avoiding deleterious side effects has proven challenging. This study investigates both intended and unintended effects of diblock copolymer nanoparticle (NP) delivery of siRNA delivery to human mesenchymal stem cells (hMSC). Specifically, siRNA delivery was investigated at a range of NP-siRNA:hMSC ratios with a focus on the effects of NP-siRNA treatment on hMSC functions. Additionally, next-generation RNA sequencing (RNA-seq) was used with enrichment analysis to observe side effects in hMSC gene expression. Results show NP-siRNA delivery is negatively correlated with hMSC density. However, higher NP-siRNA:hMSC ratios increased cytotoxicity and decreased metabolic activity. hMSC proliferation was largely unaffected by NP-siRNA treatment, except for a 3-fold reduction in hMSCs seeded at 4,000 cells/cm2. Flow cytometry reveals that apoptosis is a function of NP-siRNA treatment time and seeding density; ~14% of the treated hMSCs seeded at 8,000 cells/cm2 were annexin V+-siRNA+ 24 h after treatment, while 11% of the treated population was annexin V+-siRNA-. RNA-seq shows that NP-siRNA treatment results in transcriptomic changes in hMSCs, while pathway analysis shows upregulation of apoptosis signaling and downregulation of metabolism, cell cycle, and DNA replication pathways, as corroborated by apoptosis, metabolism, and proliferation assays. Additionally, multiple innate immune signaling pathways such as toll-like receptor (TLR), retinoic acid-inducible gene 1 (RIG-I)-like receptor, and nuclear factor-κB (NF-κB) signaling pathways are upregulated. Furthermore, and consistent with traditional siRNA immune activation, cytokine-cytokine receptor signaling was also upregulated. Overall, this study provides insight into NP-siRNA:hMSC ratios that are favorable for siRNA delivery. Moreover, NP-siRNA delivery results in side effects across the MSC transcriptome that suggest activation of the innate immunity that could alter MSC functions associated with their therapeutic potential.
2016-09-30 | GSE87497 | GEO