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Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences

Nature Biotechnology volume 17, pages 241–245 (1999)Cite this article

Abstract

Relatively low levels of expression from naturally occurring promoters have limited the use of muscle as a gene therapy target. Myogenic restricted gene promoters display complex organization usually involving combinations of several myogenic regulatory elements. By random assembly of E-box, MEF-2, TEF-1, and SRE sites into synthetic promoter recombinant libraries, and screening of hundreds of individual clones for transcriptional activity in vitro and in vivo, several artificial promoters were isolated whose transcriptional potencies greatly exceed those of natural myogenic and viral gene promoters.

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Figure 1: Strategy and design of muscle synthetic promoters.
Figure 2: Screening myogenic synthetic promoters for high transcriptional activity.
Figure 3: Synthetic promoter SPc5-12 in cultured cell lines and transgenic mice demonstrates myogenic specificity.
Figure 4: In vivo expression and activity of synthetic promoter SPc5-12.

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Acknowledgements

We thank Leigh Anne Hill and Brandon Malone for excellent technical assistance and Craig Delaughter for carefully reviewing our manuscript. We acknowledge support for this study from Applied Veterinary Systems Inc. (Houston, Texas), GeneMedicine (The Woodlands, Texas), The Texas Advanced Technology Program, and the National Space Biological Research Institute (NASA).

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Authors and Affiliations

  1. Department of Cell Biology, Baylor College of Medicine, Houston, 77030, TX

    Xuyang Li, Robert J. Schwartz & Ruxandra Draghia-Akli

  2. GeneMedicine, The Woodlands, 77318, TX

    Eric M. Eastman

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  1. Xuyang Li
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  2. Eric M. Eastman
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  4. Ruxandra Draghia-Akli
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Correspondence to Robert J. Schwartz.

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Li, X., Eastman, E., Schwartz, R. et al. Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences. Nat Biotechnol 17, 241–245 (1999). https://doi.org/10.1038/6981

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