Use of a Hybrid Adeno-Associated Viral Vector Transposon System to Deliver the Insulin Gene to Diabetic NOD Mice
Previously, we used a lentiviral vector to deliver furin-cleavable human insulin ( ) to the livers in several animal models of diabetes using intervallic infusion in full flow occlusion (FFO), with resultant reversal of diabetes, restoration of glucose tolerance and pancreatic transdifferentiation (...
Gespeichert in:
Veröffentlicht in: | Cells (Basel, Switzerland) Switzerland), 2020-10, Vol.9 (10), p.2227 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Previously, we used a lentiviral vector to deliver furin-cleavable human insulin (
) to the livers in several animal models of diabetes using intervallic infusion in full flow occlusion (FFO), with resultant reversal of diabetes, restoration of glucose tolerance and pancreatic transdifferentiation (PT), due to the expression of beta (β)-cell transcription factors (β-TFs). The present study aimed to determine whether we could similarly reverse diabetes in the non-obese diabetic (NOD) mouse using an adeno-associated viral vector (AAV) to deliver
-
± the β-TF
to the livers of diabetic mice. The traditional AAV8, which provides episomal expression, and the hybrid AAV8/
that results in transgene integration were used. Diabetic mice that received AAV8-
became hypoglycaemic with abnormal intraperitoneal glucose tolerance tests (IPGTTs). Expression of β-TFs was not detected in the livers. Reversal of diabetes was not achieved in mice that received AAV8-
-FUR and AAV8-
and IPGTTs were abnormal. Normoglycaemia and glucose tolerance were achieved in mice that received AAV8/
-
/FFO. Definitive evidence of PT was not observed. This is the first in vivo study using the hybrid AAV8/
system to treat Type 1 diabetes (T1D). However, further development is required before the system can be used for gene therapy of T1D. |
---|---|
ISSN: | 2073-4409 2073-4409 |
DOI: | 10.3390/cells9102227 |