An acidic oligopeptide displayed on AAV2 improves axial muscle tropism after systemic delivery.
BACKGROUND
The appropriate tropism of adeno-associated virus (AAV) vectors that are systemically injected is crucial for successful gene therapy when local injection is not practical. Acidic oligopeptides have been shown to enhance drug delivery to bones.


METHODS
In this study six-L aspartic acids (D6) were inserted into the AAV2 capsid protein sequence between amino acid residues 587 and 588. 129SVE mice were injected with double-stranded wild-type- (WT-) or D6-AAV2 mCherry expression vectors (3.24 x 1010 vg per animal) via the superficial temporal vein within 24 hours of birth.


RESULTS
Fluorescence microscopy and quantitative polymerase chain reaction confirmed higher levels of mCherry expression in the paraspinal and gluteus muscles in the D6-AAV2 injected mice. The results revealed that although D6-AAV2 was less efficient in the transduction of immortalized cells stronger mCherry signals were detected over the spine and pelvis by live imaging in the D6-AAV2-injected mice than were detected in the WT-AAV2-injected mice. In addition, D6-AAV2 lost the liver tropism observed for WT-AAV2.


CONCLUSIONS
An acidic oligopeptide displayed on AAV2 improves axial muscle tropism and decreases liver tropism after systemic delivery. This modification should be useful in creating AAV vectors that are suitable for gene therapy for diseases involving the proximal muscles.
Departments of Pediatrics and Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. hwuwlntu@ntu.edu.tw.
Ni-Chung
NC
Lee
Darin J
DJ
Falk
Barry J
BJ
Byrne
Thomas J
TJ
Conlon
Nathalie
N
Clement
Stacy
S
Porvasnik
Marda L
ML
Jorgensen
Mark
M
Potter
Kirsten E
KE
Erger
Rachael
R
Watson
Steven C
SC
Ghivizzani
Hung-Chuan
HC
Chiu
Yin-Hsiu
YH
Chien
Wuh-Liang
WL
Hwu