Selectively expressed RNA molecules: a new dimension in functionalized cell targeting
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PROVIDER: PRJNA1193582 | ENA |
REPOSITORIES: ENA
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Project description:Exact targeting of specific mammalian cell types or diseased cells is one of the most urgently needed prerequisites for a new generation of potent pharmaceuticals. Different approaches have been pursued, failing mainly due to a lack of specific surface markers in most cases. Developing a novel RNA-based methodology, we can now ensure exact cell targeting and simultaneously combine this with selective expression of effector proteins, thereby functionalization of the target cell for therapy, diagnostics or cell steering. The specific combination of the molecular properties of antisense technology and mRNA therapy with functional RNA secondary structures based on Nano-DMS-MaP analysis allowed us to develop selectively expressed RNA molecules for medical applications. These so-called seRNAs remain inactive in non-target cells and are only activated by partial degradation to induce translation in preselected cell types of interest. Cell type specificity and type of functionalization are easily adaptable based on a simple modular system. In proof of concept in vitro and in vivo studies we used seRNAs as a highly selective platform technology for powerful cell targeting. We effectively treat breast tumor cell clusters in mixed cell systems and reduce early brain tumors of mice without detectable side effects with just a single treatment. Our data open up new potential avenues for various therapeutic applications.
2024-12-10 | GSE283402 | GEO
Project description:We use ribosome profiling to compare the selectivity of two small molecules, PF-06446846 and PF-06378503 that inhibits translation of their target by selectively inducing ribosome-stalling in a nascent chain sequence dependent manner.
2019-03-06 | GSE121981 | GEO
Project description:Cellular response to small molecules that selectively stall protein synthesis by the ribosome
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Project description:Polyethilenimine (PEI) functionalized single walled carbon nanotubes (SWNTs) and carbon-based nanomaterials enable delivery of DNA and RNA in plants. Given the broad-scale use of PEI-functionalized nanomaterials in plants, we sought to investigate the reaction of plant tissues to treatment with PEI-SWNTs and pristine SWNTs. To this end, we infiltrated Arabidopsis thaliana leaves with pristine single walled carbon nanotubes used in RNA silencing applications (SWNTs) and polyethyleneimine-functionalized SWNTs used for plasmid DNA delivery (PEI-SWNTs). We used Arabidopsis as it is a well characterized model plant, for which genomic and detailed gene function information is readily available. To minimize the effects caused by the introduction of exogenous nucleic acids, in SWNT preparations we used single stranded RNA targeting Green Fluorescent Protein (GFP) with no target sequence in the Arabidopsis genome, and a plasmid that expresses GFP in PEI-SWNT preparations. For our experiments herein, we used ~25-50 fold higher concentrations of SWNTs and PEI-SWNTs compared to standard concentrations used in biomolecule delivery assays. Water-infiltrated plant leaves served as a negative control to distinguish between the SWNT-specific response and the response to the infiltration process itself. We performed RNA sequencing (RNA-seq) with RNA extracted from leaves two days after infiltration to identify changes in the leaf transcriptomic profile in response to the three treatments, compared to non-infiltrated leaves.
2021-12-29 | GSE172278 | GEO
Project description:Graphene oxide (GO) holds high promise for diagnostic and therapeutic applications in nanomedicine but reportedly displays immunotoxicity, underlining the need for developing functionalized GO with improved biocompatibility. Here, we study the adverse effects of GO and amino-functionalized GO (GONH2) during Caenorhabditis elegans development and ageing upon acute or chronic exposure. Chronic GO treatment throughout the C. elegans development causes decreased fecundity and a reduction of animal size, while acute treatment does not lead to any measurable physiological decline. However, RNA-Seq data reveal that acute GO exposure induces innate immune gene expression. The p38 MAP kinase, PMK-1, which is a well-established master regulator of innate immunity, protects C. elegans from chronic GO toxicity, as pmk-1 mutants show reduced tissue-functionality and facultative vivipary. In a direct comparison, GONH2 exposure does not cause detrimental effects in the wild type or in pmk-1 mutants, and the innate immune response is considerably less pronounced. Our work establishes the enhanced biocompatibility of amino-functionalized GO in a whole-organism, emphasizing its potential as biomedical nanomaterial.
2022-05-10 | GSE131070 | GEO
Project description:The environmental “light” plays a vital role in regulating the plant growth and development. Transcriptomic profilings were widely used to examine how light regulates the changes of mRNA populations at a genome-wide scale. However, it remains unclear if translational regulation represents a new dimension of gene expression regulation in response to the light signal. Through a transcriptomic comparison of steady-state and polysome-bound mRNAs, we revealed an increased translational efficiency in de-etiolating Arabidopsis seedlings. Over 3,500 genes are subjected to translational regulation whereas only about 770 genes have increased mRNA abundances in response to the light signal. This result suggests a stronger impact of translational control over transcriptomic changes during photomorphogenesis. Genes encoding ribosomal protein are preferentially regulated at the translational level, possibly contributing to the enhancement of translation efficiency as observed. We also uncovered mRNAs regulated at the translational level share characteristics of longer half-lives and shorter cDNA length. The presence of a cis-element, TAGGGTTT, in the 5’untranslated region of a transcript renders its translational regulation by light signals. Taken together, our study revealed a previously neglected aspect of gene expression regulation during Arabidopsis photomorphogenesis. The identities and molecular signatures associated with mRNAs regulated at the translational level also offer new directions to perform mechanistic studies of light-trigged translational enhancement in Arabidopsis. Three biological replicates for 4-d-old etiolated seedlings with or without 0. 5 h or 4 h of white-light treatment.
2012-07-10 | E-GEOD-29657 | biostudies-arrayexpress
Project description:The environmental “light” plays a vital role in regulating the plant growth and development. Transcriptomic profilings were widely used to examine how light regulates the changes of mRNA populations at a genome-wide scale. However, it remains unclear if translational regulation represents a new dimension of gene expression regulation in response to the light signal. Through a transcriptomic comparison of steady-state and polysome-bound mRNAs, we revealed an increased translational efficiency in de-etiolating Arabidopsis seedlings. Over 3,500 genes are subjected to translational regulation whereas only about 770 genes have increased mRNA abundances in response to the light signal. This result suggests a stronger impact of translational control over transcriptomic changes during photomorphogenesis. Genes encoding ribosomal protein are preferentially regulated at the translational level, possibly contributing to the enhancement of translation efficiency as observed. We also uncovered mRNAs regulated at the translational level share characteristics of longer half-lives and shorter cDNA length. The presence of a cis-element, TAGGGTTT, in the 5’untranslated region of a transcript renders its translational regulation by light signals. Taken together, our study revealed a previously neglected aspect of gene expression regulation during Arabidopsis photomorphogenesis. The identities and molecular signatures associated with mRNAs regulated at the translational level also offer new directions to perform mechanistic studies of light-trigged translational enhancement in Arabidopsis.
2012-07-11 | GSE29657 | GEO
Project description:We have employed whole genome microarray expression to distinguish the effect of diversely functionalized magnetic silica nanoparticles on human HepaRG cells. Cells were exposed in vitro, and datasets of differentially expressed genes were identified for NPs versus control samples.
2017-09-23 | GSE98236 | GEO
Project description:Functionalized carbon nanotube toxicity in Arabidopsis leaves
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Project description:Targeting somatostatin receptors by functionalized mesoporous silica nanoparticles.
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