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<lom:identifier>
  
<lom:catalog>DOI</lom:catalog>

  
<lom:entry>
  
<lom:langstring xml:lang="x-none">10.1016/j.omtm.2023.03.003</lom:langstring>

  
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</lom:identifier>

  
<lom:title>
  
<lom:langstring xml:lang="en">Prolonged activity of the transposase helper may raise safety concerns during DNA transposon-based gene therapy</lom:langstring>

  
</lom:title>

  
<lom:description>
  
<lom:langstring xml:lang="en">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 one 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.</lom:langstring>

  
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<lom:language>eng</lom:language>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Tyrosinemia Type-I; Sleeping-Beauty Transposase; Piggybac Transposon; Murine Model; Hepatic-Dysfunction; Site Selection; Mouse-Liver; Methylations; Mutagenesis; Expression</lom:langstring>

  
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<lom:datetime>2023-10-17T08:49:47.100Z</lom:datetime>

  
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N:Imre;Gergely;
FN:Gergely Imre
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N:Haracska;Lajos;
FN:Lajos Haracska
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N:Mátés;Lajos;
FN:Lajos Mátés
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N:Nagy;István;
FN:István Nagy
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N:Barta;Endre;
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N:Rülicke;Thomas;
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N:Pintér;Lajos;
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N:Sükösd;Farkas;
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N:Nagy;László G.;
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N:Kovács;Anita;
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N:Kopasz;Anna Georgina;
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N:Ahmed Abdullah;Khaldoon Sadiq;
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N:Bálint;Balázs;
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N:Germán;Péter;
FN:Péter Germán
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N:Hegedűs;Zoltán;
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N:Blastyák;András;
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N:Pankotai-Bodó;Gabriella;
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N:Vásárhelyi;Bálint Márk;
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N:Hudoba;Liza;
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N:Hudoba;Liza;
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N:Karkas;Réka;
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N:Nagy;Andrea;
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N:Latinovics;Dóra;
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N:Drubi;Andrea Bakné;
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N:Takács;Bertalan;
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N:Czipa;Erik;
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