Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Int J Med Sci 2016; 13(4):286-291. doi:10.7150/ijms.14152 This issue Cite

Research Paper

Enhancing Transgene Expression from Recombinant AAV8 Vectors in Different Tissues Using Woodchuck Hepatitis Virus Post-Transcriptional Regulatory Element

Lizheng Wang1, Zixuan Wang1, Fangfang Zhang1, Rui Zhu1, Jinpeng Bi1, Jiaxin Wu1, Haihong Zhang1, Hui Wu1, Wei Kong1,2, Bin Yu1✉, Xianghui Yu1,2✉

1. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China
2. Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China

✉ Corresponding authors: School of Life Sciences, Jilin University, Changchun 130012, China. Fax: +86 0431 85167751. E-mail addresses: yubinedu.cn (B. Yu), xianghuiedu.cn (X. Yu)

Citation:
Wang L, Wang Z, Zhang F, Zhu R, Bi J, Wu J, Zhang H, Wu H, Kong W, Yu B, Yu X. Enhancing Transgene Expression from Recombinant AAV8 Vectors in Different Tissues Using Woodchuck Hepatitis Virus Post-Transcriptional Regulatory Element. Int J Med Sci 2016; 13(4):286-291. doi:10.7150/ijms.14152. https://www.medsci.org/v13p0286.htm
Other styles

File import instruction

Abstract

Adeno-associated virus (AAV) vectors have been utilized extensively in gene therapy and gene function studies, as strong transgene expression is a prerequisite for positive outcomes. AAV8 was reported as the most efficient AAV serotype for transduction of the liver, brain and muscle compared with other serotypes. However, AAV8-mediated transduction of human hepatocytes is rather poor with approximately 20-fold lower efficiency compared with that of mouse hepatocytes. Therefore, we applied the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) to enhance AAV8-mediated transgene expression driven by a combination promoter (CAG promoter) with a CMV-IE enhancer and chicken beta-actin promoter for a more efficient viral vector. Transgene expression from recombinant AAV8 (rAAV8) vectors harboring a red fluorescent protein (RFP) reporter gene with or without WPRE were evaluated in vitro and in vivo. The results demonstrated that WPRE improved AAV8-mediated RFP expression in different cell lines with clear increases of transgene expression in the liver, brain or muscle of animals. The findings of this study will help to substantially reduce the quantity of viral particles that must be injected in order to reach a therapeutic level of transgene expression in gene therapy. Consequently, such dose reductions may lessen the potential risks associated with high doses of viral vectors.

Keywords: adeno-associated viral vector, WPRE, transgene expression, gene therapy

Citation styles

APA
Wang, L., Wang, Z., Zhang, F., Zhu, R., Bi, J., Wu, J., Zhang, H., Wu, H., Kong, W., Yu, B., Yu, X. (2016). Enhancing Transgene Expression from Recombinant AAV8 Vectors in Different Tissues Using Woodchuck Hepatitis Virus Post-Transcriptional Regulatory Element. International Journal of Medical Sciences, 13(4), 286-291. https://doi.org/10.7150/ijms.14152.

ACS
Wang, L.; Wang, Z.; Zhang, F.; Zhu, R.; Bi, J.; Wu, J.; Zhang, H.; Wu, H.; Kong, W.; Yu, B.; Yu, X. Enhancing Transgene Expression from Recombinant AAV8 Vectors in Different Tissues Using Woodchuck Hepatitis Virus Post-Transcriptional Regulatory Element. Int. J. Med. Sci. 2016, 13 (4), 286-291. DOI: 10.7150/ijms.14152.

NLM
Wang L, Wang Z, Zhang F, Zhu R, Bi J, Wu J, Zhang H, Wu H, Kong W, Yu B, Yu X. Enhancing Transgene Expression from Recombinant AAV8 Vectors in Different Tissues Using Woodchuck Hepatitis Virus Post-Transcriptional Regulatory Element. Int J Med Sci 2016; 13(4):286-291. doi:10.7150/ijms.14152. https://www.medsci.org/v13p0286.htm

CSE
Wang L, Wang Z, Zhang F, Zhu R, Bi J, Wu J, Zhang H, Wu H, Kong W, Yu B, Yu X. 2016. Enhancing Transgene Expression from Recombinant AAV8 Vectors in Different Tissues Using Woodchuck Hepatitis Virus Post-Transcriptional Regulatory Element. Int J Med Sci. 13(4):286-291.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use