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A retroviral vector suitable for ultrasound image-guided gene delivery to mouse brain

Gene Therapy volume 19, pages 396–403 (2012)Cite this article

Abstract

Gene transfer to the early-stage embryonic brain using the ultrasound image-guided gene delivery (UIGD) technique has proven to be valuable for investigating brain development. Thus far, this technology has been restricted to the study of embryonic neurogenesis. When this technique is designed to be employed for the study in adult animals, a long-term stable gene expression will be required. We attempted to develop a retroviral vector suitable for expressing exogenous genes in the brains of postnatal and adult mice in the context of the UIGD technique. Retroviral vectors containing four different long terminal repeats (LTRs) (each from Moloney murine leukemia virus (MoMLV), murine stem cell virus (MSCV), myeloproliferative sarcoma virus (MPSV) and spleen focus-forming virus (SFFV)) were compared using the well-known CE vector having the EF1α internal promoter as a control. The MS vector containing MSCV LTR produced a higher viral titer and a higher level of gene expression than other vectors including CE. The MS vector drove the gene expression in cultured neural stem cells for 3 weeks. Furthermore, the MS vector could efficiently deliver the gene to the mouse central nervous system, as transgene expression was found in various regions of the brains and spinal cords as well as in all major neural cell types. The data from an in vivo luciferase imaging analysis showed that the gene expression from the MS vector was sustainable for almost 3 months. Our data suggested that the MS vector would be suitable to construct mice containing the transgene expressed in the brain or spinal cord in a quick and cost-effective manner.

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Acknowledgements

This work was supported by the grant given to S Kim's university laboratory by Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology (#2011K000287), in which ViroMed Co. Ltd is a participating company.

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Authors and Affiliations

  1. Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Seoul, Korea

    J Jang & S Kim

  2. School of Life Science and Biotechnology, Sungkyunkwan University, Seoul, Korea

    K Yoon

  3. Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea

    D W Hwang

  4. WCU Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea

    D S Lee

  5. School of Biological Sciences, Seoul National University, Seoul, Korea

    S Kim

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  1. J Jang
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  2. K Yoon
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Correspondence to S Kim.

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Jang, J., Yoon, K., Hwang, D. et al. A retroviral vector suitable for ultrasound image-guided gene delivery to mouse brain. Gene Ther 19, 396–403 (2012). https://doi.org/10.1038/gt.2011.120

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