Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Common AAV gene therapy vectors show nonselective transduction of ex vivo human brain tissue

ABSTRACT: We have adapted an ex vivo organotypic model to evaluate AAV transduction properties in living slices of human brain tissue. Using single-nucleus RNA sequencing, we found that common AAV vectors show broad transduction of normal cell types, with protein expression most apparent in astrocytes; this work introduces a pipeline for identifying and optimizing AAV gene therapy vectors in human brain samples.

ORGANISM(S): Homo sapiens

PROVIDER: GSE292722 | GEO | 2025/06/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Common AAV gene therapy vectors show nonselective transduction of ex vivo human brain tissue

Project description:Common AAV gene therapy vectors show nonselective transduction of ex vivo human brain tissue

| PRJNA1241144 | ENA

Triple vectors expand AAV transfer capacity in the retina

Project description:Maddalena et al. showed that the limited DNA transfer capacity (~4.7kb) of adeno associated viral (AAV) vectors can be expanded up to 14kb with triple AAV vectors for the efficient expression of the therapeutic CDH23 (10.1kb) and ALMS1 (12.5kb) genes.

2017-12-20 | GSE107173 | GEO

Casein kinase 2 activity is a host restriction factor for AAV transduction

Project description:Despite rapid progress in the development of new therapies based on adeno-associated viral vectors (AAVs) in recent years, successful transduction of the human heart remains challenging. So far, the mechanisms that impede AAV transduction, especially in humans are poorly understood, hampering the introduction of new, effective gene therapy strategies. Therefore, the aim of this study was to identify and overcome the main cellular barriers to successful transduction in the heart, using iPSC-derived cardiomyocytes (iPSC-CMs), cardiac fibroblasts (iPSC-CFs), and primary endothelial cells (HAECs) to model vector-host interactions. Through phosphoproteome analysis of AAV9-transduced iPSC-CFs we established that casein kinase 2 (CK2) signalling is one of the most significantly affected pathways upon AAV exposure. Importantly, transient inhibition of CK2 activity with silmitasertib substantially enhanced the transduction rate of AAV2, AAV6 and AAV9 in all tested cell types (iPSC-CMs, iPSC-CFs and HAECs), demonstrating the versatility of this approach. CK2 inhibition improved the trafficking of AAVs through the cytoplasm and impaired DNA-damage response through destabilisation of Mre11, sensor of dsDNA breaks, that directly binds the ITRs of the vector genome. Silmitasertib treatment also allowed for improvement of transgene expression in already transduced iPSC-CFs, which retain AAV genomes in a functional, but probably silent form. Furthermore, our analysis revealed that AAV transduction may interfere with RNA processing pathways, identifying matrin-3 as a necessary factor for efficient transgene delivery. In summary, presented study provides new insights into the current understanding of the host-AAV vector interaction, identifying CK2 activity as a key barrier to efficient transduction and transgene expression, therefore offering a promising strategy to improve the outcome of AAV-based therapies in the future.

2024-03-28 | PXD040035 | Pride

AAV vectors trigger neurotoxic DNA damage responses and STING-dependent inflammation in human CNS cells [scRNAseq_dataset2]

Project description:Adeno-associated viral (AAV) vector gene therapy is gaining ground as a treatment option for genetic neurodegenerative diseases tha currently have no cure. Nonetheless, significant toxicity and severe adverse events are emerging in recent clinical trials through mechanisms that remain unclear. We have modelled here AAV-mediated neurotoxicity in the context of the human brain taking advantage of human induced pluripotent stem cell-based technologies. We have used single-cell RNA sequencing technologies to interrogate vector-induced cell-intrinsic innate immune mechanisms that could contribute to neurotoxicity in 3D brain sphheroids transduced with AAV vectors at different time-points and harvested at two different time-points.

2025-03-11 | GSE253822 | GEO

AAV vectors trigger neurotoxic DNA damage responses and STING-dependent inflammation in human CNS cells [scRNAseq_dataset1]

Project description:Adeno-associated viral (AAV) vector gene therapy is gaining ground as a treatment option for genetic neurodegenerative diseases tha currently have no cure. Nonetheless, significant toxicity and severe adverse events are emerging in recent clinical trials through mechanisms that remain unclear. We have modelled here AAV-mediated neurotoxicity in the context of the human brain taking advantage of human induced pluripotent stem cell-based technologies. We have used single-cell RNA sequencing technologies to interrogate vector-induced cell-intrinsic innate immune mechanisms that could contribute to neurotoxicity in mixed 2D neuron-glial cultures transduced with AAV vectors at different time-points and harvested at two different time-points.

2025-03-11 | GSE253821 | GEO

AAV vectors trigger neurotoxic DNA damage responses and STING-dependent inflammation in human CNS cells [scRNAseq_dataset3]

Project description:Adeno-associated viral (AAV) vector gene therapy is gaining ground as a treatment option for genetic neurodegenerative diseases tha currently have no cure. Nonetheless, significant toxicity and severe adverse events are emerging in recent clinical trials through mechanisms that remain unclear. We have modelled here AAV-mediated neurotoxicity in the context of the human brain taking advantage of human induced pluripotent stem cell-based technologies. We have used single-cell RNA sequencing technologies to interrogate vector-induced cell-intrinsic innate immune mechanisms that could contribute to neurotoxicity in mixed 2D neuron-glial cultures transduced with AAV vectors at different time-points and harvested at two different time-points.

2025-03-11 | GSE253823 | GEO

Extra-HEK293-AAV: Transcriptomics of modified HEK293 cell line for higher productivity of biologics (e.g. viral vectors, AAV)

Project description:The human EXT1 gene has been knockdown in HEK293 cells to improve their performance in producing viral vectors such as AAV. This work compares the gene expression for the wildtype and kd_EXT1 cells, in adherent and suspension cultures.

2023-11-25 | GSE248262 | GEO

Characterization of microglia polarization states under targeted AAV transduction using bulk and single cell RNA sequencing

Project description:The study of microglia biology and the development of microglia-based gene therapies are in urgent need of efficient and safe vehicles for microglia transgene delivery. To address this, we developed adeno-associated virus (AAV) variants that mediate efficient in vitro and in vivo microglia transduction via directed evolution of the AAV capsid protein. To assess the effect of AAV transduction on microglia, we carried out bulk RNAseq in primary microglia and found that microglia transduced by AAV remain close to homeostatic state. Furthermore, single-cell RNA sequencing showed that the AAV-MG variants mediate safe in vivo transgene delivery without inducing microglia immune activation. These AAV variants should facilitate the applications of various genetically-encoded sensors and effectors in studying microglia-related biology and therapeutic interventions.

2022-04-06 | GSE197743 | GEO

Triple vectors expand AAV transfer capacity in the retina

Project description:Triple vectors expand AAV transfer capacity in the retina

| PRJNA419212 | ENA

A truncated reverse transcriptase enhances prime editing by split AAV vectors

Project description:To investigate if the truncated PE can be dilivered by dual AAV8 vectors for in vivo prime editing. We injected the dual AAV8 into 10-week-old C57BL/6J mice . Livers were isolated 4 weeks after injection and next generation sequencing showed an average of 1.4% and 5.4% precise prime editing with the low and high AAV doses, respectively (Figure 4D ). This demonstrates that PECO-Mini can be efficiently delivered by dual AAVs for in vivo prime editing.

2022-06-09 | GSE205532 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data