Targeted delivery of Chil3/Chil4 siRNA to alveolar macrophages using ternary complexes composed of HMG and oligoarginine micelles

Cell-type-specific genes involved in disease can be effective therapeutic targets; therefore, the development of a cell-type-specific gene delivery system is essential.

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In vivo cell type-specific gene delivery with retroviral vectors that display single chain antibodies

Gene Therapy ◽

10.1038/sj.gt.3301043 ◽

1999 ◽

Vol 6 (12) ◽

pp. 1982-1987 ◽

Cited By ~ 23

Author(s):

A Jiang ◽

R Dornburg ◽

R Dornburg

Keyword(s):

Gene Delivery ◽

Retroviral Vectors ◽

Specific Gene ◽

Cell Type ◽

Single Chain ◽

Single Chain Antibodies ◽

Cell Type Specific

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Injectable Thermo-Sensitive Chitosan Hydrogel Containing CPT-11-Loaded EGFR-Targeted Graphene Oxide and SLP2 shRNA for Localized Drug/Gene Delivery in Glioblastoma Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms21197111 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7111 ◽

Cited By ~ 2

Author(s):

Yu-Jen Lu ◽

Yu-Hsiang Lan ◽

Chi-Cheng Chuang ◽

Wan-Ting Lu ◽

Li-Yang Chan ◽

...

Keyword(s):

Graphene Oxide ◽

Gene Delivery ◽

Drug Release ◽

Delivery System ◽

Targeted Delivery ◽

Drug Formulation ◽

Treatment Modalities ◽

Gene Delivery System ◽

Optimal Drug

In this study, we aimed to develop a multifunctional drug/gene delivery system for the treatment of glioblastoma multiforme by combining the ligand-mediated active targeting and the pH-triggered drug release features of graphene oxide (GO). Toward this end, we load irinotecan (CPT-11) to cetuximab (CET)-conjugated GO (GO-CET/CPT11) for pH-responsive drug release after endocytosis by epidermal growth factor receptor (EGFR) over-expressed U87 human glioblastoma cells. The ultimate injectable drug/gene delivery system was designed by co-entrapping stomatin-like protein 2 (SLP2) short hairpin RNA (shRNA) and GO-CET/CPT11 in thermosensitive chitosan-g-poly(N-isopropylacrylamide) (CPN) polymer solution, which offers a hydrogel depot for localized, sustained delivery of the therapeutics after the in situ formation of CPN@GO-CET/CPT11@shRNA hydrogel. An optimal drug formulation was achieved by considering both the loading efficiency and loading content of CPT-11 on GO-CET. A sustained and controlled release behavior was found for CPT-11 and shRNA from CPN hydrogel. Confocal microscopy analysis confirmed the intracellular trafficking for the targeted delivery of CPT-11 through interactions of CET with EGFR on the U87 cell surface. The efficient transfection of U87 using SLP2 shRNA was achieved using CPN as a delivery milieu, possibly by the formation of shRNA/CPN polyplex after hydrogel degradation. In vitro cell culture experiments confirmed cell apoptosis induced by CPT-11 released from acid organelles in the cytoplasm by flow cytometry, as well as reduced SLP2 protein expression and inhibited cell migration due to gene silencing. Finally, in vivo therapeutic efficacy was demonstrated using the xenograft of U87 tumor-bearing nude mice through non-invasive intratumoral delivery of CPN@GO-CET/CPT11@shRNA by injection. Overall, we have demonstrated the novelty of this thermosensitive hydrogel to be an excellent depot for the co-delivery of anticancer drugs and siRNA. The in situ forming hydrogel will not only provide extended drug release but also combine the advantages offered by the chitosan-based copolymer structure for siRNA delivery to broaden treatment modalities in cancer therapy.

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Distinct CoREST complexes act in a cell-type-specific manner

Nucleic Acids Research ◽

10.1093/nar/gkz1050 ◽

2019 ◽

Author(s):

Igor Mačinković ◽

Ina Theofel ◽

Tim Hundertmark ◽

Kristina Kovač ◽

Stephan Awe ◽

...

Keyword(s):

Gene Expression ◽

Germ Line ◽

Protein Complexes ◽

Specific Gene ◽

S2 Cells ◽

Cell Type ◽

Specific Gene Expression ◽

Genome Wide ◽

A Cell ◽

Cell Type Specific

Abstract CoREST has been identified as a subunit of several protein complexes that generate transcriptionally repressive chromatin structures during development. However, a comprehensive analysis of the CoREST interactome has not been carried out. We use proteomic approaches to define the interactomes of two dCoREST isoforms, dCoREST-L and dCoREST-M, in Drosophila. We identify three distinct histone deacetylase complexes built around a common dCoREST/dRPD3 core: A dLSD1/dCoREST complex, the LINT complex and a dG9a/dCoREST complex. The latter two complexes can incorporate both dCoREST isoforms. By contrast, the dLSD1/dCoREST complex exclusively assembles with the dCoREST-L isoform. Genome-wide studies show that the three dCoREST complexes associate with chromatin predominantly at promoters. Transcriptome analyses in S2 cells and testes reveal that different cell lineages utilize distinct dCoREST complexes to maintain cell-type-specific gene expression programmes: In macrophage-like S2 cells, LINT represses germ line-related genes whereas other dCoREST complexes are largely dispensable. By contrast, in testes, the dLSD1/dCoREST complex prevents transcription of germ line-inappropriate genes and is essential for spermatogenesis and fertility, whereas depletion of other dCoREST complexes has no effect. Our study uncovers three distinct dCoREST complexes that function in a lineage-restricted fashion to repress specific sets of genes thereby maintaining cell-type-specific gene expression programmes.

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Inducible cell-specific mouse models for paired epigenetic and transcriptomic studies of microglia and astroglia

Communications Biology ◽

10.1038/s42003-020-01418-x ◽

2020 ◽

Vol 3 (1) ◽

Cited By ~ 1

Author(s):

Ana J. Chucair-Elliott ◽

Sarah R. Ocañas ◽

David R. Stanford ◽

Victor A. Ansere ◽

Kyla B. Buettner ◽

...

Keyword(s):

Gene Expression ◽

Affinity Purification ◽

Regulation Of Gene Expression ◽

Cell Types ◽

Tissue Level ◽

Cell Phenotype ◽

Specific Gene ◽

Cell Type ◽

A Cell ◽

Cell Type Specific

AbstractEpigenetic regulation of gene expression occurs in a cell type-specific manner. Current cell-type specific neuroepigenetic studies rely on cell sorting methods that can alter cell phenotype and introduce potential confounds. Here we demonstrate and validate a Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) approach for temporally controlled labeling and isolation of ribosomes and nuclei, and thus RNA and DNA, from specific central nervous system cell types. Analysis of gene expression and DNA modifications in astrocytes or microglia from the same animal demonstrates differential usage of DNA methylation and hydroxymethylation in CpG and non-CpG contexts that corresponds to cell type-specific gene expression. Application of this approach in LPS treated mice uncovers microglia-specific transcriptome and epigenome changes in inflammatory pathways that cannot be detected with tissue-level analysis. The NuTRAP model and the validation approaches presented can be applied to any brain cell type for which a cell type-specific cre is available.

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Dual-functionalized calcium carbonate based gene delivery system for efficient gene delivery

RSC Advances ◽

10.1039/c4ra05468g ◽

2014 ◽

Vol 4 (73) ◽

pp. 38623-38629 ◽

Cited By ~ 11

Author(s):

Chao-Qun Wang ◽

Meng-Qing Gong ◽

Jin-Long Wu ◽

Ren-Xi Zhuo ◽

Si-Xue Cheng

Keyword(s):

Calcium Carbonate ◽

Gene Delivery ◽

Delivery System ◽

Gene Transfection ◽

Cell Penetrating Peptide ◽

Gene Delivery System ◽

Dna Nanoparticles ◽

Efficient Gene ◽

Cell Penetrating ◽

A Cell

Dual-functionalized KALA/PS/CaCO3/DNA nanoparticles containing a cell penetrating peptide (KALA) and protamine sulfate (PS) could effectively mediate gene transfection at a low DNA concentration.

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Effect of Sequence-Directed Nucleosome Disruption on Cell-Type-Specific Repression by α2/Mcm1 in the Yeast Genome

Eukaryotic Cell ◽

10.1128/ec.00105-06 ◽

2006 ◽

Vol 5 (11) ◽

pp. 1925-1933 ◽

Cited By ~ 22

Author(s):

Nobuyuki Morohashi ◽

Yuichi Yamamoto ◽

Shunsuke Kuwana ◽

Wataru Morita ◽

Heisaburo Shindo ◽

...

Keyword(s):

Dna Sequences ◽

Nucleosome Positioning ◽

Yeast Genome ◽

Specific Gene ◽

Cell Type ◽

Chromatin Structural ◽

A Cell ◽

Cell Type Specific ◽

Acting In Concert ◽

Modest Effect

ABSTRACT In Saccharomyces cerevisiae, a-cell-specific genes are repressed in MATα cells by α2/Mcm1, acting in concert with the Ssn6-Tup1 corepressors and the Isw2 chromatin remodeling complex, and nucleosome positioning has been proposed as one mechanism of repression. However, prior studies showed that nucleosome positioning is not essential for repression by α2/Mcm1 in artificial reporter plasmids, and the importance of the nucleosome positioning remains questionable. We have tested the function of positioned nucleosomes through alteration of genomic chromatin at the a-cell-specific gene BAR1. We report here that a positioned nucleosome in the BAR1 promoter is disrupted in cis by the insertion of diverse DNA sequences such as poly(dA) · poly(dT) and poly(dC-dG) · poly(dC-dG), leading to inappropriate partial derepression of BAR1. Also, we show that isw2 mutation causes loss of nucleosome positioning in BAR1 in MATα cells as well as partial disruption of repression. Thus, nucleosome positioning is required for full repression, but loss of nucleosome positioning is not sufficient to relieve repression completely. Even though disruption of nucleosome positioning by the cis- and trans-acting modulators of chromatin has a modest effect on the level of transcription, it causes significant degradation of the α-mating pheromone in MATα cells, thereby affecting its cell type identity. Our results illustrate a useful paradigm for analysis of chromatin structural effects at genomic loci.

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