Next Article in Journal
Detection of Multiple Variants of Grapevine Fanleaf Virus in Single Xiphinema index Nematodes
Previous Article in Journal
Genetic Characterization and Molecular Evolution of Urban Seoul Virus in Southern China
Article

Chimeric Capsid Proteins Impact Transduction Efficiency of Haploid Adeno-Associated Virus Vectors

1
Gene Therapy Center, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
2
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
4
Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, NC 27510, USA
*
Author to whom correspondence should be addressed.
Received: 15 October 2019 / Revised: 27 November 2019 / Accepted: 6 December 2019 / Published: 9 December 2019
(This article belongs to the Section Animal Viruses)
Our previous studies have demonstrated that haploid AAV vectors made from capsids of two different serotypes induced high transduction and prevented serotype-specific antibody binding. In this study, we explored the transduction efficiency of several haploid viruses, which were made from the VP1/VP2 of one serotype and VP3 of another compatible serotype. After systemic injection of 2 × 1010 vg of AAV vectors into mice, the haploid AAV vectors, composed of VP1/VP2 from serotypes 8 or 9, and VP3 from AAV2, displayed a two to seven-fold increase in liver transduction compared with those of parental AAV2 vectors. Furthermore, a chimeric AAV2/8 VP1/VP2 with N-terminus of VP1/VP2 from AAV2 and C-terminus (VP3 domain) from AAV8 was constructed, and produced the haploid vector 28m-2VP3 with AAV2 VP3. The haploid 28m-2VP3 vector showed a five-fold higher transduction than that of the vectors composed solely of AAV2 VPs. Remarkably, the 28m-2VP3 vectors also induced a significant increase in transgene expression compared to the vectors composed of AAV8 VP1/VP2 with AAV2 VP3. The results suggest that the difference in the VP1/VP2 N-terminal region between AAV2 and AAV8 may allow better “communication” between the VP1/VP2 N-terminus of AAV2 with its cognate VP3. Similarly, the haploid vectors, VP1/VP2 from serotypes 8 or 9 and VP3 from AAV3, achieved higher transductions in multiple tissue types beyond typical tropism compared with those of AAV3 vectors. Consistently, higher vector genome copy numbers were detected in these tissues, indicating that an incorporation of non-cognate VP1/VP2 might influence the cellular tropism of the haploid vectors. However, there was no significant difference or even decreased transductions when compared with those of parental AAV8 or AAV9 vectors. In summary, these studies provide insight into current development strategies of AAV vectors that can increase AAV transduction across multiple tissues. View Full-Text
Keywords: AAV; gene therapy; enhanced transduction; haploid vector AAV; gene therapy; enhanced transduction; haploid vector
Show Figures

Figure 1

MDPI and ACS Style

Chai, Z.; Zhang, X.; Dobbins, A.L.; Frost, E.A.; Samulski, R.J.; Li, C. Chimeric Capsid Proteins Impact Transduction Efficiency of Haploid Adeno-Associated Virus Vectors. Viruses 2019, 11, 1138. https://0-doi-org.brum.beds.ac.uk/10.3390/v11121138

AMA Style

Chai Z, Zhang X, Dobbins AL, Frost EA, Samulski RJ, Li C. Chimeric Capsid Proteins Impact Transduction Efficiency of Haploid Adeno-Associated Virus Vectors. Viruses. 2019; 11(12):1138. https://0-doi-org.brum.beds.ac.uk/10.3390/v11121138

Chicago/Turabian Style

Chai, Zheng, Xintao Zhang, Amanda L. Dobbins, Ellie A. Frost, R. J. Samulski, and Chengwen Li. 2019. "Chimeric Capsid Proteins Impact Transduction Efficiency of Haploid Adeno-Associated Virus Vectors" Viruses 11, no. 12: 1138. https://0-doi-org.brum.beds.ac.uk/10.3390/v11121138

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop