Precision RNAi using synthetic shRNAmir target sites
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA903783 | ENA |
REPOSITORIES: ENA
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Project description:Precision RNAi using synthetic shRNAmir target sites
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Project description:Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient, inducible, and reversible suppression of any gene upon introduction of a synthetic target sequence into non-coding transcript regions. ARTi establishes a scalable loss-of-function tool with full control over on- and off-target effects.
2023-07-04 | GSE218617 | GEO
Project description:Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient, inducible, and reversible suppression of any gene upon introduction of a synthetic target sequence into non-coding transcript regions. ARTi establishes a scalable loss-of-function tool with full control over on- and off-target effects.
2023-07-04 | GSE218404 | GEO
Project description:Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient and inducible suppression of any gene upon introduction of a synthetic target sequence into non-coding transcript regions. ARTi establishes a scalable loss-of-function tool with full control over on- and off-target effects.
| S-EPMC10409502 | biostudies-literature
Project description:Synthetic lethality-mediated precision oncology via the tumor transcriptome
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Project description:Epigenome analysis of dnmt target sites
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Project description:Synthetic lethality exploits the genetic vulnerabilities of cancer cells enabling, a targeted, precision approach to treat cancer. Synthetic lethal discovery approaches have led to clinical successes of PARP inhibitors and the progression of several next-generation therapeutic targets such as WRN, USP1, PKMYT1, POLQ, and PRMT5 into the clinic. To date, however, most discovery efforts in the synthetic lethal space have focused on DNA repair. Here, we show, for the first time in humans, a frequent synthetic lethal interaction between two complexes of the translational repair pathway, PELO/HBS1L and the superkiller (SKI) complex. In distinct genetic contexts, either in 9p21.3 (FOCAD) deleted or MSI-H tumors, we found that phenotypically destabilized SKI complex leads to dependence on the PELO/HBS1L ribosomal rescue complex. We estimate that 20% of all tumors have a destabilized SKI complex. The concomitant loss of PELO in a SKI destabilized tumor drives an unfolded protein stress response, cell cycle arrest, and robust tumor growth inhibition. Furthermore, we demonstrate that the loss of HBS1L phenocopies PELO loss, presenting a second potential therapeutic target within the rescue complex. Our results indicate that PELO/HBS1L represent novel therapeutic targets whose dependence converges upon SKI complex destabilization, a common phenotypic biomarker in diverse genetic contexts and a significant patient population.
2024-10-14 | GSE261804 | GEO
Project description:Nm-seq maps 2'-O-methylation sites in human mRNA with base precision The ribose of rna nucleotides can be 2′-O-methylated (nm). despite advances in high-throughput detection, the inert chemical nature of nm still limits sensitivity and precludes mapping in mrna. We leveraged the differential reactivity of 2′-O-methylated and 2′-hydroxylated nucleosides to periodate oxidation to develop nm-seq, a sensitive method for transcriptome-wide mapping of nm with base precision. nm-seq uncovered thousands of nm sites in human mrna with features suggesting functional roles.
2017-05-15 | GSE90164 | GEO
Project description:We performed STARR-seq with synthetic libraries (synSTARR-seq) in GR18 cell line (derived from U2OS ATTC:HTB-96, stably transfected with an expression construct for GR), upon glucocorticoid (dexamethasone) or vehicle (ethanol) treatment. The synthetic libraries are variants of the glucocorticoid receptor binding sites (GBS). The "GBS half site" library contains 8 consecutive randomized nucleotides within the core binding sites, while the "Cgt/Sgk library" contains 5 consecutive randomized nucleotides on the flank of the GBS.
2018-10-29 | E-MTAB-6737 | biostudies-arrayexpress
Project description:To examine off-target effects of RAD17 RNAi by shRNA transduction, expression profilling was performed.
2013-06-03 | E-MTAB-1535 | biostudies-arrayexpress