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Intraperitoneal AAV9-shRNA inhibits target expression in neonatal skeletal and cardiac muscles.

Abstract：

:Systemic injections of AAV vectors generally transduce to the liver more effectively than to cardiac and skeletal muscles. The short hairpin RNA (shRNA)-expressing AAV9 (shRNA-AAV9) can also reduce target gene expression in the liver, but not enough in cardiac or skeletal muscles. Higher doses of shRNA-AAV9 required for inhibiting target genes in cardiac and skeletal muscles often results in shRNA-related toxicity including microRNA oversaturation that can induce fetal liver failure. In this study, we injected high-dose shRNA-AAV9 to neonates and efficiently silenced genes in cardiac and skeletal muscles without inducing liver toxicity. This is because AAV is most likely diluted or degraded in the liver than in cardiac or skeletal muscle during cell division after birth. We report that this systemically injected shRNA-AAV method does not induce any major side effects, such as liver dysfunction, and the dose of shRNA-AAV is sufficient for gene silencing in skeletal and cardiac muscle tissues. This novel method may be useful for generating gene knockdown in skeletal and cardiac mouse tissues, thus providing mouse models useful for analyzing diseases caused by loss-of-function of target genes.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Mayra A,Tomimitsu H,Kubodera T,Kobayashi M,Piao W,Sunaga F,Hirai Y,Shimada T,Mizusawa H,Yokota T

doi

10.1016/j.bbrc.2011.01.009

subject

Has Abstract

pub_date

2011-02-11 00:00:00

pages

204-9

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(11)00019-2

journal_volume

405

pub_type

杂志文章

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