Delivery of non-viral naked DNA vectors to liver in small weaned pigs by hydrodynamic retrograde intrabiliary injection.
DNA-vector
bile duct
hydrodynamic intrabiliary injection
liver gene therapy
non-viral
pig
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
10 Mar 2022
10 Mar 2022
Historique:
received:
07
07
2021
accepted:
16
01
2022
entrez:
25
2
2022
pubmed:
26
2
2022
medline:
26
2
2022
Statut:
epublish
Résumé
Hepatic gene therapy by delivering non-integrating therapeutic vectors in newborns remains challenging due to the risk of dilution and loss of efficacy in the growing liver. Previously we reported on hepatocyte transfection in piglets by intraportal injection of naked DNA vectors. Here, we established delivery of naked DNA vectors to target periportal hepatocytes in weaned pigs by hydrodynamic retrograde intrabiliary injection (HRII). The surgical procedure involved laparotomy and transient isolation of the liver. For vector delivery, a catheter was placed within the common bile duct by enterotomy. Under optimal conditions, no histological abnormalities were observed in liver tissue upon pressurized injections. The transfection of hepatocytes in all tested liver samples was observed with vectors expressing luciferase from a liver-specific promoter. However, vector copy number and luciferase expression were low compared to hydrodynamic intraportal injection. A 10-fold higher number of vector genomes and luciferase expression was observed in pigs using a non-integrating naked DNA vector with the potential for replication. In summary, the HRII application was less efficient (i.e., lower luciferase activity and vector copy numbers) than the intraportal delivery method but was significantly less distressful for the piglets and has the potential for injection (or re-injection) of vector DNA by endoscopic retrograde cholangiopancreatography.
Identifiants
pubmed: 35211639
doi: 10.1016/j.omtm.2022.01.006
pii: S2329-0501(22)00007-9
pmc: PMC8829443
doi:
Types de publication
Journal Article
Langues
eng
Pagination
268-279Informations de copyright
© 2022 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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