Molecular Therapy
Volume 14, Issue 1, July 2006, Pages 45-53
Journal home page for Molecular Therapy

Article
Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8

https://doi.org/10.1016/j.ymthe.2006.03.014Get rights and content
Under a Creative Commons license
open archive

Abstract

It has been recently shown that recombinant adeno-associated virus serotype 8 (rAAV8) is a robust alternative serotype vector that overcomes many of the limitations of rAAV2 and transduces various tissues efficiently and globally through systemic vector administration. AAV9 is a serotype newly isolated from human tissues, but our knowledge of the biology of rAAV9 in vivo is currently limited. Here, we demonstrate by a series of comprehensive side-by-side experiments with rAAV8 and 9 vectors delivered via different routes or at various doses in mice that rAAV9 vectors share the robustness of rAAV8, i.e., (1) very high liver transduction efficiency irrespective of whether vectors are administered intravascularly or extravascularly and (2) substantial transduction in the heart, skeletal muscle, and pancreas by peripheral vein injection. Importantly, rAAV9 transduced myocardium 5- to 10-fold higher than rAAV8, resulting in over 80% cardiomyocyte transduction following tail vein injection of as low as 1.0 × 1011 particles per mouse. Thus rAAV9, as well as rAAV8, is a robust vector for gene therapy applications and rAAV9 is superior to rAAV8 specifically for cardiac gene delivery by systemic vector administration.

Keywords

adeno-associated virus
serotype
gene therapy
heart
myocardium
skeletal muscle
pancreas
liver
systemic delivery
subcutaneous injection

Cited by (0)