Table 1.
Summary of mouse studies that observed or investigated HCC formation after rAAV gene delivery
| Publication | AAV serotype | Genome configuration | Enhancer/promoter (∗promoters only) | Transgene | Route of delivery | Dose | Time of treatment | Loci with integration(s) associated with HCC |
|---|---|---|---|---|---|---|---|---|
| Donsante 200142 Donsante 200746 |
2 | SS | CMV/CBA | GUSB | superficial temporal vein | 1 × 1014 vg/kg | neonatal | Rian |
| Bell 200547 | 1,2,5,7,8,9, others | SS | Alb, CBA, SV40, TBG, Z12∗ | A1AT, EGFP, Epo, FIX, LacZ, LDLR, TF1 | portal vein tail vein |
3 × 109-1 × 1012 vg/mouse | 6–8 weeks | none |
| Bell 200648 Zhong 201349 |
2,7,8,9 | SS | AMPB/TBG | Oct, LacZ | portal vein | 3 × 109-1 × 1012 vg/mouse | 9–11 weeks | Tax1bp1, Rian |
| Reiss 201150 | 1/2 | SS | CMV/CBA | MOCS1 | intrahepatic | 1–3 × 109 vg/pup | neonatal | none |
| Embury 200851 | 2 | SS | CBA∗ (WPRE) | mPah | portal vein | 3.7 × 109-7.3 × 1013 vg/mouse | 10–14 weeks | none |
| Li 201152 | 2 | SS | APOE/hAAT | FIX | portal vein | 5 × 1012-1 × 1014 vg/kg | 4 weeks | none |
| Wang 201253 | 2 | SS | CMV/CBA | Homology Arms to Rian | temporal vein | 3 × 109 vg/pup | neonatal | Rian |
| Rosas 201254 | Rh74 | SC | CMV, CBA∗ | GFP, null | tail vein | 5 × 1010 vg/mouse | 8–12 weeks | Hras1, Sos1, Fgf3 |
| Kao 201355 | 8 | SS | APOE/hAAT | FIX-WT, FIX-Triple, FIX-Padua | tail vein | 1.6 × 1012-2 × 1010 vg/mouse | adult | none |
| Chandler 201556 | 2,8,9 | SS | AMPB/TBG CMV/CBA APOE/hAAT |
hMUT, mMut, GFP | intrahepatic | 7 × 1012-1 × 1014 vg/kg | neonatal | Rian |
| Walia 201557 | 9 | SS | CMV/CMV | HexB, LacZ | superficial temporal vein | 2.5 × 1014 vg/kg | neonatal | Rian |
| Kang 201958 | 9 | SS | TBG | G6PC, ZFN | tail vein | 4.8 × 1012-1.3 × 1013 vg/kg | adult | Rian |
| Dalwadi 202159 | DJ | SS | CMV/CAG | Homology Arms to Rian, tdTomato | superficial temporal vein | 3 × 1010 vg/pup 8 × 1011 vg/adult |
neonatal adults |
Rian |
| Li 202160 | 9 | SS | CMV/CBA | GALC | intracranial or intrathecal | 2.7 × 1010 vg/pup | neonatal | Rian, FoxP1, Tusc3, Magi1, Kcnh1, Akap13 |
HCC, hepatic carcinoma; rAAV, recombinant adeno-associated virus; SS, single stranded; SC, self-complementary; CMV, cytomegalovirus; CBA, chicken beta-actin; Alb, albumin; TBG, thyroxin binding globulin; WPRE, woodchuck hepatitis virus post-transcriptional regulatory element; TBG, thyroxin binding globulin; APOE, apolipoprotein E; hAAT, human alpha-1 antitrypsin; CAG, cytomegalovirus enhancer/chicken beta-actin promoter.
Adapted from Chandler, 2017.25