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Series GSE212895 Query DataSets for GSE212895
Status Public on Mar 09, 2023
Title Treatment of TT1 mice with transposon-based gene therapy
Organism Mus musculus
Experiment type Other
Summary DNA transposon-based gene delivery vectors represent a promising new branch of randomly integrating vector development for gene therapy. For the side-by-side evaluation of the piggyBac and Sleeping Beauty systems - the only DNA transposons currently employed in clinical trials - during therapeutic intervention, we treated the mouse model of Tyrosinemia type I. with liver-targeted gene delivery using both transposon vectors. For genome-wide mapping of transposon insertion sites we developed a new Next Generation Sequencing procedure called Streptavidin-Based Enrichment Sequencing, which allowed us to identify approximately 1 million integration sites for both systems. We revealed that a high proportion of piggyBac integrations are clustered in hot regions and found that they are frequently recurring at the same genomic positions among treated animals, indicating that the genome-wide distribution of Sleeping Beauty-generated integrations is closer to random. We also revealed that the piggyBac transposase protein exhibits prolonged activity, which predicts the risk of oncogenesis by generating chromosomal double-strand breaks. Safety concerns associated with prolonged transpositional activity draw attention to the importance of squeezing the active state of the transposase enzymes into a narrower time window.
Overall design In vivo transposon-based gene therapy was applied to treat Fah KO mice using either the PB or the SB vector system. At the end of the monitoring periods, genomic DNA was isolated from the PB- and the SB-treated livers. Streptavidin-Based Enrichment Sequencing (SBE-seq) was applied to identify genomic vector insertion sites.
Contributor(s) Jaksa G, Takács B, Imre G, Mátés L
Citation(s) 37025950
BioProject PRJNA605684
Submission date Sep 08, 2022
Last update date May 02, 2023
Contact name Lajos Mates
Organization name Biological Research Centre
Department Institute of Genetics
Lab Laboratory of Cancer Genome Research
Street address Temesvari krt. 62.
City Szeged
ZIP/Postal code H-6726
Country Hungary
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (30)
GSM6560668 Sequencing of therapeutic transposon insertions from TT1 mouse liver [ PB1_liver]
GSM6560669 Sequencing of therapeutic transposon insertions from TT1 mouse liver [ PB2_liver]
GSM6560670 Sequencing of therapeutic transposon insertions from TT1 mouse liver [ PB3_liver]

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Supplementary file Size Download File type/resource
GSE212895_PBmerged_1_12_liver_unique_integrations_filtered.bed.gz 5.1 Mb (ftp)(http) BED
GSE212895_RAW.tar 17.6 Mb (http)(custom) TAR (of BED)
GSE212895_SBmerged_1_12_liver_unique._integrations._filtered.bed.gz 5.3 Mb (ftp)(http) BED
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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