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Inhalation of ACE2-expressing lung spheroid cell exosomes provides prophylactic protection against SARS-CoV-2

ABSTRACT: Inhalation of ACE2-expressing lung spheroid cell exosomes provides prophylactic protection against SARS-CoV-2

PROVIDER: PRJNA1051566 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27185769_1.fastq.gz	Fastqsanger.gz
	SRR27185769_2.fastq.gz	Fastqsanger.gz
	SRR27185770_1.fastq.gz	Fastqsanger.gz
	SRR27185770_2.fastq.gz	Fastqsanger.gz
	SRR27185771_1.fastq.gz	Fastqsanger.gz

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Inhalation of ACE2-expressing lung spheroid cell exosomes provides prophylactic protection against SARS-CoV-2

Project description:Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity pose the urgency for developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction is a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) could function as a prophylactic agent to bind and neutralize SARS-CoV-2 and protect the host against SARS-CoV-2 infection. Inhalation of LSC-Exo facilitates their deposition and biodistribution throughout the whole lung in a female mouse model. We show that LSC-Exo blocks the interaction of SARS-CoV-2 with host cells in vitro and in vivo by neutralizing the virus. LSC-Exo treatment protected hamsters from SARS-CoV-2-induced disease and reduced viral loads. Furthermore, LSC-Exo intercept the entry of multiple SARS-CoV-2 variant pseudoviruses in female mice and show comparable or equal potency against the wild-type strain, demonstrating that LSC-Exo may act as broad-spectrum protectant against existing and emerging virus variants.

2024-01-13 | GSE249987 | GEO

Inhalation of ACE2-expressing lung spheroid cell exosomes provides prophylactic protection against SARS-CoV-2

Project description:We demonstrated that lung spheroid cell derived exosomes (LSC-Exo) carry the parental cell’s ACE2 that are able to target lung, intercept SARS-CoV-2 entry, confer protection against SARS-CoV-2 infection. This LSC-Exo prophylaxis paradigm would not be limited by viral evolution, showing great potential for emerged SARS-CoV-2 variants, including those that are yet to emerge.

2024-01-13 | PXD047542 | Pride

Regulation by the homologous Ace2 and Swi5 factors of Saccharomyces cerevisiae

Project description:The homologous Ace2 and Swi5 transcription factors of Saccharomyces cerevisiae have identical DNA-binding domains, and both are cell cycle regulated. There are common target genes, as well as genes activated only by Ace2 and other genes activated only by Swi5. Keywords: genetic modification RNA was isolated from four strains: wild type, ace2 gene deletion, swi5 gene deletion, and the ace2 swi5 double gene deletion. RNAs from the three mutant strains were compared to wild type RNA in a microarray hybridization experiment.

2008-05-13 | E-GEOD-11380 | biostudies-arrayexpress

Effects of ACE2 on BMPR2 mutation-mediated defects in gene expression

Project description:BMPR2 mutation causes pulmonary arterial hypertension (PAH); ACE2 treatment can resolve established BMPR2-mediated PAH. The purpose of this study was to uncover the molecular mechanism behind this. Four groups: +/- ACE2 and +/- BMPR2 transgene, two arrays each, each array a pool of three animals.

2010-08-24 | E-GEOD-21583 | biostudies-arrayexpress

The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2

Project description:The rapid and escalating spread of SARS coronavirus 2 (SARS-CoV-2) poses an immediate public health emergency, and no approved therapeutics or vaccines are currently available. The viral spike protein S binds membrane-tethered ACE2 on host cells in the lungs to initiate molecular events that ultimately release the viral genome intracellularly. The extracellular protease domain of ACE2 inhibits cell entry of both SARS and SARS-2 coronaviruses by acting as a soluble decoy for receptor binding sites on S, and is a promising candidate for therapeutic and prophylactic development. Using deep mutagenesis, variants of ACE2 are identified with increased binding to the receptor binding domain of S at a cell surface. Mutations are found across the protein-protein interface and also at buried sites where they are predicted to enhance folding and presentation of the interaction epitope. The mutational landscape offers a preliminary blueprint for engineering high affinity ACE2 receptors to meet this unprecedented challenge.

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Inhalation of Lung Spheroid Cell-Secreted Factors and Exosomes Promotes Therapeutic Lung Repair in Rodent Models of Pulmonary Fibrosis

Project description:Idiopathic pulmonary fibrosis (IPF) is a fatal form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue becomes stiff and losses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung spheroid cell-derived conditioned media (LSC-CM) and exosomes (LSC-EXO) to treat different rodent models of lung injury and fibrosis. Inhalation treatment was given for seven consecutive days via a nebulizer for clinical relevance. Results revealed that LSC-CM and LSC-EXO treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure, decreasing collagen accumulation, and myofibroblast proliferation. In addition, LSC-CM and LSC-EXOs exhibited superior therapeutic benefits than their counterparts derived from bone marrow mesenchymal stem cells. LSC-CM and LSC-EXOs provide promising therapeutic options for pulmonary fibrosis.

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High resistance barrier and prophylactic protection in preclinical models of SARS-CoV-2 with two siRNA combination

Project description:RNA interference is a natural antiviral mechanism that could be harnessed to combat SARS-CoV-2 infection by targeting and destroying the viral RNA. We identified potent lipophilic small-interfering RNA (siRNA) conjugates targeting highly conserved regions of the SARS-CoV-2 outside of the spike-encoding region capable of achieving ≥3-log viral reduction. Serial passaging studies demonstrated that a two-siRNA combination prevented development of resistance compared to a single-siRNA approach. Viral resistance to single siRNA treatment occurred due to emergence of point mutations at critical positions required for siRNA-mediated target binding and cleavage, which led to a loss of siRNA efficacy. With a two-siRNA combination, emergence of mutations within the siRNA binding site was abolished. When delivered intranasally, two-siRNA combination protected Syrian hamsters from weight loss and lung pathology by viral infection upon prophylactic administration but not following onset of infection. Together, the data support potential utility of RNAi as a prophylactic approach with high resistance barrier to counteract SARS-CoV-2 emergent variants and complement vaccination. Most importantly, given that the siRNAs can be rapidly developed from a new pathogen sequence, this strategy has implications as a new type of preventive medicines that may protect against future coronavirus pandemics.

2024-12-04 | GSE276876 | GEO

Inhalation of Lung Spheroid Cell-Secreted Factors and Exosomes Promotes Therapeutic Lung Repair in Rodent Models of Pulmonary Fibrosis

Project description:Inhalation of Lung Spheroid Cell-Secreted Factors and Exosomes Promotes Therapeutic Lung Repair in Rodent Models of Pulmonary Fibrosis

| PRJNA561784 | ENA

Smoke Inhalation and NIST SRM Lipidomics

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2021-11-12 | MSV000088372 | MassIVE

Gene expression analysis of glioblastoma spheroid cultures II

Project description:Microarray-based gene expression analysis identified genes differentially expressed in 10 glioblastoma spheroid cultures compared to a non-neoplastic spheroid culture isolated from the bulbus olfactorius In this study, a set of 10 glioblastoma spheroid cultures was used to acquire expression profiles of a total of 17 093 transcripts, leading to the identification of differentially expressed genes compared to a non-neoplastic brain spheroid culture

2010-02-12 | E-GEOD-16666 | biostudies-arrayexpress

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