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Piecing together more efficient gene expression

Nature Biotechnology volume 17, pages 224–225 (1999)Cite this article

In this issue, Robert Schwartz2 and colleagues describe an approach to evolve more effective muscle-specific transcription promoters by mixing and matching operator elements from four distinct muscle-specific promoters (Fig. 1B). They succeeded in creating synthetic promoters that are eightfold more effective than the corresponding natural promoters, both in vitro and in vivo. This approach to novel promoter construction should prove to be a useful new tool to enhance tissue-specific expression for both therapeutic and transgenic applications.

Early gene therapy vectors made use of viral promoters to drive gene expression because complex viral genomes had been studied intensely and their compact nature made them easier to manipulate than most eukaryotic cellular promoters. Experience with ex vivo gene therapy approaches, however, has shown that viral promoters are often inactivated by unknown mechanisms3. Promoters of endogenous cellular genes often fare no better. Some constitutive "housekeeping" promoters have shown some activity4, although in these cases expression of the gene was often weak. These problems, inherent to the use of natural promoters, have spurred investigators to try to engineer synthetic promoters tailored for specific applications.

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Figure 1: Genetic engineering approaches to tailor gene expression.

References

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Authors and Affiliations

  1. research associates, Laboratory of Genetics, The Salk Institute , 10010 N. Torrey Pines Road, La Jolla, 92037, CA

    Nikunj V. Somia & Tal Kafri

  2. professor at the Laboratory of Genetics, The Salk Institute , 10010 N. Torrey Pines Road, La Jolla, 92037, CA

    Inder M. Verma

Authors
  1. Nikunj V. Somia
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  2. Tal Kafri
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  3. Inder M. Verma
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Somia, N., Kafri, T. & Verma, I. Piecing together more efficient gene expression. Nat Biotechnol 17, 224–225 (1999). https://doi.org/10.1038/6962

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