Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Extensive length and homology dependent chimerism in pool-packaged AAV libraries

ABSTRACT: Adeno-associated viruses (AAVs) have emerged as the foremost gene therapy delivery vehicles due to their versatility, durability and safety profile. Here we demonstrate extensive chimerism among complex AAV libraries that are packaged as a pool. The observed chimerism is length- and homology-dependent but capsid-independent, in some cases affecting >60% of packaged AAV genomes. These results have important implications for the design and deployment of functional AAV libraries in research and clinical settings.

ORGANISM(S): synthetic construct

PROVIDER: GSE284548 | GEO | 2025/01/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Extensive length and homology dependent chimerism in pool-packaged AAV libraries

Project description:Extensive length and homology dependent chimerism in pool-packaged AAV libraries

| PRJNA1199511 | ENA

packaged drinking water

Project description:packaged drinking water Metagenome

| PRJNA940339 | ENA

D4 and C2 assessed for chimerism and germline transmission

Project description:Two independent ES cell lines (D4 and C2) were assessed for chimerism and germline transmission. Although these lines were able to produce chimerism at early passage, no germ line transmission was seen. After passaging in a proprietary medium and subcloning by detaching loosely connected cells and culturing in the recommended medium, both lines experienced an increase in potential as evidenced by an enhanced ability to go germ line. Analysis of early passage, and late passage detached and attached cells will allow the determination of genes that may be implicated in the increase of potential seen in these cells. Note: additional replicates may be added at a later date. Keywords: embryonic stem cells, chimerism, germline transmission

2006-01-24 | GSE4087 | GEO

Characterization of Residual MicroRNAs in AAV Vector Batches Produced in HEK293 Mammalian Cells and Sf9 Insect Cells

Project description:With more than 130 clinical trials and eight approved gene therapy products, AAVs stand as one of the most popular vehicles to deliver therapeutic DNA in vivo. One critical quality attribute analyzed in AAV batches is the presence of residual DNA, as it could pose genotoxic risks or induce immune responses. Surprisingly, the presence of small cell‑derived RNAs, such as micro‑RNAs, has not been previously investigated. In this study, we examined the presence of miRNAs in purified AAV batches produced in mammalian or in insect cells. Our findings revealed that miRNAs were present in all batches, regardless of the production cell line or capsid serotype (2 and 8). Quantitative assays indicated that miRNAs were co‑purified with the rAAV particles in a proportion correlated with their abundance in the production cells. The level of residual miRNAs was reduced via an immunoaffinity chromatography purification process including a tangential flow filtration step or by RNase treatment, suggesting that most miRNA contaminants are likely non encapsidated into AAV particles. In summary, we demonstrate, for the first time, that miRNAs are co-purified with AAV particles. Further investigations are required to determine whether these miRNAs could interfere with the safety or efficacy of AAV-mediated gene therapy.

2024-06-30 | GSE270691 | GEO

Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

Project description:Viral genetictools that target specificbraincell types could transform basicneuroscienceand targeted gene therapy. Here, we use comparative open chromatin analysis to identify thousands of human-neocortical-subclass-specific putative enhancers from across the genome tocontrol gene expressionin adeno-associated virus (AAV) vectors. The cellular specificity of reporter expression from enhancer-AAVs is established by molecular profiling after systemic AAV delivery in mouse. Over 30% of enhancer-AAVs produce specific expression in the targeted subclass, including both excitatory and inhibitory subclasses. We present a collection ofParvalbumin(PVALB) enhancer-AAVs that show highly enriched expression not only in cortical PVALB cells but also in some subcortical PVALB populations. Five vectors maintain PVALB-enriched expression in primateneocortex. These results demonstrate how genome-wide open chromatin data mining and cross-species AAV validation can be used to create the next generation of non-species-restricted viral genetic tools.

2023-06-27 | GSE235997 | GEO

Evaluation of the effects of bowel cleansing of Jing Chang Pre-packaged food

Project description:Interventions: A:JingChang Pre-packaged Product No.1 (4g Konjac Powder);G:JingChang Pre-packaged Product No.2 (2g Konjac Powder);F:JingChang Pre-packaged Product No.3 (1g Konjac Powder);D:Give competing formulations currently available on the market;E:Self prepared diet Primary outcome(s): Clarity of stools after bowel cleansing Study Design: Parallel

| 105843 | ecrin-mdr-crc

Vacuum packaged beef and lamb

Project description:Vacuum packaged beef and lamb Targeted loci

| PRJNA580325 | ENA

A Self-Complementary AAV Proviral Plasmid System to Reduce Aberrant Cross-Packaging and ITR Promoter Activity in AAV Vector Preparations (Long-read)

Project description:Adeno-associated viral vectors (AAV) are a leading delivery system for gene therapy in animal models and humans. With several FDA-approved AAV gene therapies on the market, issues related to vector manufacturing have become increasingly important. In this study, we focused on potentially toxic DNA contaminants that can arise from AAV proviral plasmids, the raw materials required for manufacturing recombinant AAV in eukaryotic cells. Typical AAV proviral plasmids are circular DNAs containing a therapeutic gene cassette flanked by natural AAV inverted terminal repeat (ITR) sequences, and a plasmid backbone carrying prokaryotic sequences required for plasmid replication and selection in bacteria. While the majority of AAV particles package the intended therapeutic payload, some capsids instead package the bacterial sequences located on the proviral plasmid backbone. Since ITR sequences also have promoter activity, potentially toxic bacterial open reading frames can be produced in vivo, thereby representing a safety risk. In this study, we describe a new AAV proviral plasmid for vector manufacturing that (1) significantly decreases cross-packaged bacterial sequences; (2) increases correctly packaged AAV payloads; and (3) blunts ITR-driven transcription of cross-packaged material to avoid expressing potentially toxic bacterial sequences. This system may help improve the safety of AAV vector products.

2024-07-26 | GSE272650 | GEO

A Self-Complementary AAV Proviral Plasmid System to Reduce Aberrant Cross-Packaging and ITR Promoter Activity in AAV Vector Preparations (Short-read)

2024-07-26 | GSE272649 | GEO

scAAVengr, a transcriptome-based pipeline for quantitative ranking of engineered AAVs with single-cell resolution

Project description:Adeno-associated virus (AAV)-mediated gene therapies are rapidly advancing to the clinic, and AAV engineering has resulted in vectors with increased ability to deliver therapeutic genes. Although the choice of vector is critical, quantitative comparison of AAVs, especially in large animals, remains challenging. Here, we developed an efficient single-cell AAV engineering pipeline (scAAVengr) to simultaneously quantify and rank efficiency of competing AAV vectors across all cell types in the same animal. To demonstrate proof-of-concept for the scAAVengr workflow, we quantified – with cell-type resolution – the abilities of naturally occurring and newly engineered AAVs to mediate gene expression in primate retina following intravitreal injection. A top performing variant identified using this pipeline, K912, was used to deliver SaCas9 and edit the rhodopsin gene in macaque retina, resulting in editing efficiency similar to infection rates detected by the scAAVengr workflow. scAAVengr was then used to identify top-performing AAV variants in mouse brain, heart and liver following systemic injection. These results validate scAAVengr as a powerful method for development of AAV vectors.

2021-10-19 | GSE161645 | 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