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Study on AAV-mediated gene therapy for diabetes in humanized liver mouse to predict efficacy in humans.

Abstract：

:Most in vivo studies on the conversion to insulin-producing cells with AAV carrying PDX1 gene are performed in rodents. However, there is little information regarding Adeno-associated virus (AAV) carrying PDX1 gene transduced to human liver in vivo because accidental death caused by unpredicted factors cannot be denied, such as the hypoglycemic agent troglitazone with hepatic failure. Here we aim to confirm insulin secretion from human liver transduced with AAV carrying PDX1 gene in vivo and any secondary effect using a humanized liver mouse. As the results, AAV2-PG succeeded to improve the hyperglycemia of STZ-induced diabetic humanized liver mice. Then, the analysis of humanized liver mice revealed that the AAV2-PG was more transducible to humanized liver area than to mouse liver area. In conclusion, the humanized liver mouse model could be used to examine AAV transduction of human hepatocytes in vivo and better predict clinical transduction efficiency than nonhumanized mice.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Hashimoto H,Mizushima T,Ogura T,Kagawa T,Tomiyama K,Takahashi R,Yagoto M,Kawai K,Chijiwa T,Nakamura M,Suemizu H

doi

10.1016/j.bbrc.2016.08.104

subject

Has Abstract

pub_date

2016-09-23 00:00:00

pages

1254-60

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(16)31360-2

journal_volume

478

pub_type

杂志文章

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