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Antisense oligonucleotides modified with a boron cluster and a cholesterol moiety (B-ASO-LNA-CHOL)

ABSTRACT: B-ASO-LNA-CHOL EGFR inhibitor

PROVIDER: PRJEB96297 | ENA |

REPOSITORIES: ENA

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Knockdown of circular RNAs using LNA-modified antisense oligonucleotides

Project description:Circular RNAs (circRNAs) constitute an abundant class of covalently closed non-coding RNA molecules that are formed by backsplicing from eukaryotic protein-coding genes. Recent studies have shown that circRNAs can act as microRNA or protein decoys as well as transcriptional regulators. However, the functions of most circRNAs are still poorly understood. Because circRNA sequences overlap with their linear parent transcripts, depleting specific circRNAs without affecting host gene expression remains a challenge. Here, we assessed the utility of LNA-modified antisense oligonucleotides (ASOs) to knock down circRNAs for loss-of-function studies. We identified 5807 circRNAs in total RNA sequencing data from 4 liver cancer cell lines and used the back splice junction (BSJ) sequences of 7 validated circRNAs as target sites for designing different LNA-modified ASOs for circRNA knockdown. We found that while most RNase H-dependent gapmer ASOs mediate effective knockdown of their target circRNAs, some gapmers reduce the levels of the linear parent transcript and may also cause degradation of unintended off-targets. The circRNA targeting specificity can be enhanced using design-optimized gapmer ASOs or LNA/DNA mixmer ASOs, which display potent and specific circRNA knockdown with a minimal effect on the host genes or predicted off-targets. In summary, our results demonstrate that LNA-modified ASOs complementary to BSJ sequences mediate robust knockdown of circRNAs in vitro and, thus, represent a useful tool to explore the biological roles of circRNAs in loss-of-function studies in cultured cells and animal models.

2022-11-01 | GSE145592 | GEO

Knockdown of circular RNAs using LNA-modified antisense oligonucleotides

Project description:Knockdown of circular RNAs using LNA-modified antisense oligonucleotides

| PRJNA607690 | ENA

Targeting GI-SINE (Growth inducing B2-SINE) RNA in DRG neurons by Antisense Oligonucleotides (ASO)

Project description:We identified 2 specific motifs that are enriched in GI-SINE RNA expressed in sciatic-nerve injured DRG neurons compared to non-regulated B2-SINE RNAs. We designed a mix of 5 ASOs (21nt phosphorothioate DNA with LNA-flanks) that target these motifs and transfected those into cultured dorsal root ganglia (DRG) neurons. Control ASO was based on a 21nt non-targetting sequence from shControl backbone (addgene plasmid #85741). Primary DRG neurons were transfected using Dharmafect-4 with ASO at 50nM final concentration 1 hour after plating. Cultures were processed for RNA extraction 48h after transfection for RNA sequencing to identify changes in B2-SINE expression.

2025-05-16 | GSE262153 | GEO

Expression analysis of mice hepatic NMuLi cells treated LNA gapmer ASO containing nucleobase modification

Project description:Antisense oligonucleotide (ASO) has the potential to induce hybridization-dependent effects by inadvertent binding of ASOs to RNA with sequences similar to that of the target RNA. In the present study, we examined the effects of the nucleobase derivatives introduced into the gapmer ASOs on gene expression. We performed microarray analysis using NMuLi cells (mouse liver-derived cells) treated with LNA gapmer ASO containing nucleobase modification.

2022-07-12 | GSE197166 | GEO

Gene expression profile of modified gapmer antisense oligonucleotides treated mouse liver

Project description:To investigate gene expression change induced by modified gapmer antisense oligonucleotides, we performed transcriptome analysis of Scarb1 ASO or PBS treated mouse livers.

2025-03-28 | GSE289964 | GEO

PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates.

Project description: Not available

| S-EPMC3277239 | biostudies-literature

Structure Activity Relationships of α-L-LNA Modified Phosphorothioate Gapmer Antisense Oligonucleotides in Animals.

Project description: Not available

| S-EPMC3499693 | biostudies-other

Expression analysis of mice hepatic NMuLi cells treated LNA gapmer ASO containing nucleobase modification

Project description:Expression analysis of mice hepatic NMuLi cells treated LNA gapmer ASO containing nucleobase modification

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The transcriptome profile after antisense L1 ASO treatment [ssRNA-Seq]

Project description:We performed RNA-seq assay in Scramble ASO and antisense Mus1_L1 ASO treated AML12 cells to reveal the trscriptiome associated with MATR3 protein. The libraries were constructed by ribosome-depleted and strand-specific kits.

2023-06-28 | GSE228646 | GEO

Highly Potent GalNAc-Conjugated Tiny LNA Anti-miRNA-122 Antisense Oligonucleotides.

Project description: Not available

| S-EPMC8228246 | biostudies-literature