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Lee NC, Falk DJ, Byrne BJ, et al. An acidic oligopeptide displayed on AAV2 improves axial muscle tropism after systemic delivery. Genet Vaccines Ther. 2012;10(1):3doi: 10.1186/1479-0556-10-3.
Lee, N. C., 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., Chien, Y. H., & Hwu, W. L. (2012). An acidic oligopeptide displayed on AAV2 improves axial muscle tropism after systemic delivery. Genetic vaccines and therapy, 10(1), 3. https://doi.org/10.1186/1479-0556-10-3
Lee, Ni-Chung, et al. "An acidic oligopeptide displayed on AAV2 improves axial muscle tropism after systemic delivery." Genetic vaccines and therapy vol. 10,1 (2012): 3. doi: https://doi.org/10.1186/1479-0556-10-3
Lee NC, Falk DJ, Byrne BJ, Conlon TJ, Clement N, Porvasnik S, Jorgensen ML, Potter M, Erger KE, Watson R, Ghivizzani SC, Chiu HC, Chien YH, Hwu WL. An acidic oligopeptide displayed on AAV2 improves axial muscle tropism after systemic delivery. Genet Vaccines Ther. 2012 Jun 18;10(1):3. doi: 10.1186/1479-0556-10-3. PMID: 22709483; PMCID: PMC3416570.
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Genet Vaccines Ther. 2012 Jun 18;10(1):3. doi: 10.1186/1479-0556-10-3.

An acidic oligopeptide displayed on AAV2 improves axial muscle tropism after systemic delivery.

Genetic vaccines and therapy

Ni-Chung Lee, Darin J Falk, Barry J Byrne, Thomas J Conlon, Nathalie Clement, Stacy Porvasnik, Marda L Jorgensen, Mark Potter, Kirsten E Erger, Rachael Watson, Steven C Ghivizzani, Hung-Chuan Chiu, Yin-Hsiu Chien, Wuh-Liang Hwu

Affiliations

  1. Departments of Pediatrics and Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. [email protected].

PMID: 22709483 PMCID: PMC3416570 DOI: 10.1186/1479-0556-10-3

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 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.

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