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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Cell specific gene silencing by lipid-siRNA conjugates in mouse central nervous system barriers

ABSTRACT: Dysfunctional brain barriers contribute to the pathophysiology of chronic CNS diseases, but few non-viral technologies are established that effectively target these interfaces. In this work, we developed a lipid-siRNA conjugate that modulate gene expression in brain barriers such as the blood-brain-barrier (BBB), which describes the restrictive properties of brain microvascular endothelial cells (BMEC), as well as the blood-CSF-barrier (BCSFB) formed by the choroid plexus. We showed robust delivery and knockdown in brain endothelial cells and the choroid plexus. In this experiment, we used single cell RNA sequencing to determine which CNS cell types exhibit siRNA-mediated gene silencing. To that end, we administered a 20 mg/kg intravenous dose of our lipid siRNA conjugate targeting Ppib or a non-targeting control. Brains were dissociated into single cells and processed for sequencing using PIPseq workflow. We found that gene silencing was specific to the brain barriers; we only detected knockdown in brain endothelial and choroid plexus epithelial cells.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Andrew Kjar

PROVIDER: E-MTAB-14840 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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