An acidic oligopeptide displayed on AAV2 improves axial muscle tropism after systemic delivery
Journal
Genetic Vaccines and Therapy
Journal Volume
10
Pages
3
Date Issued
2012
Author(s)
Falk D.J.
Byrne B.J.
Conlon T.J.
Clement N.
Porvasnik S.
Jorgensen M.L.
Potter M.
Erger K.E.
Watson R.
Ghivizzani S.C.
Chiu H.-C.
Abstract
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 10 10 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. ? 2012 Lee et al.; licensee Biomed Central Ltd.
SDGs
Other Subjects
amino acid; aspartic acid; aspartic acid parvovirus vector 2; oligopeptide; parvovirus vector; unclassified drug; animal cell; animal experiment; animal model; animal tissue; article; controlled study; drug mechanism; fluorescence microscopy; human; human cell; mouse; muscle disease; newborn; nonhuman; viral gene therapy; Adeno-associated virus; Animalia; Miridae; Mus
Type
journal article