Fig. 4: LV-huFAH shows a benign integration profile in pig hepatocytes after in vivo exposure portal vein delivery. | Nature Communications

Fig. 4: LV-huFAH shows a benign integration profile in pig hepatocytes after in vivo exposure portal vein delivery.

From: In vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions

Fig. 4: LV-huFAH shows a benign integration profile in pig hepatocytes after in vivo exposure portal vein delivery.The alternative text for this image may have been generated using AI.

a Biodistribution of LV-FAH as determined by selective PCR amplification of long terminal repeats over 48 h, 60 days, and 337 days in animals that received portal vein (No. 169, No. 162, No. 166, No. 167, respectively) and systemic injection of LV-FAH. Numbers represent the following tissues: (1) right lateral liver, (2) right medial liver, (3) left lateral liver, (4) left medial liver, (5) spleen, (6) kidney, (7) pancreas, (8) duodenum, (9) jejunum, (10) ileum, (11) colon, (12) mesenteric lymph node, (13) heart, (14) right lung, (15) left lung, (16) mediastinal lymph node, (17) testes or ovaries, (18) brain. This experiment was repeated with three primer pairs with similar results. b Chromosomal maps of integration events found in No. 162, No. 166, and No. 167 livers. c Relative LV integration across exons, introns, and intragenic regions. d Relative LV integration frequency across the genome as stratified by expression level. P-values for d-f are based on a two-tailed z-test with no adjustment for multiple comparisons. e Relative LV integration frequency showing preference for non-CpG island sites, when adjusted for prevalence in the genome. f Relative LV integration frequency showing no preference tumor-coding genes. g Relative integration frequency as stratified by distance from transcription start site. h Lentiviral vector copy number found in liver at the time of necropsy. i Comparison of LV-FAH integration sites in the livers of No. 167 and No. 166 show high similarity, with 307 common integrations. Gene Set Enrichment Analysis (GSEA) demonstrated no hits in No. 166, but enrichment of the PI3K-Akt and TGFb signaling pathways in No. 167.

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