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  • Letter to the Editor
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Comment on the use of the cre/loxP recombinase system for gene therapy vectors

Gene Therapy volume 7, page 1706 (2000)Cite this article

In the recent editorial ‘Radiation to control gene expression’, Stackhouse and Buchsbaum1 gave an excellent summary of the published research on the use of radiation to target gene therapy for cancer. They also comment on several issues that will have to be addressed before this approach can have a practical application. In the article, they outline our own work2 on a ‘molecular switch’ to enhance therapeutic gene expression following a comparatively low induction dose of radiation. Commenting on the use of the cre/loxP recombination system, they state: ‘The hypothesis that once cre recombinase is produced it will continue to create a functional therapeutic transcript has not been tested. The durability of expression of the cre gene and the stability of the cre enzyme will be critical determinants for the continued expression of the therapeutic gene’. In fact, the basis of the system we describe obviates the need for the continued expression of cre via the radiation-responsive promoter. Consequently, a brief review of the mechanism we have utilised is appropriate to clarify the situation.

The cre enzyme catalyzes the site-specific recombination of DNA between 34bp loxP sites.3 The result of recombination is governed by the relative orientation of the loxP sites.4 A segment of ‘spacer’ DNA flanked by loxP sites (‘floxed’) which are unidirectionally orientated, can then be excised by intramolecular loxP recombination via the action of the cre protein.

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References

  1. Stackhouse MA, Bauchbaum DJ . Radiation to contol gene expression Gene Therapy 2000 7: 1085–1086

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  2. Scott SD et al. A radiation-controlled molecular switch for use in gene therapy of cancer Gene Therapy 2000 7: 1121–1125

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  3. Sternberg N, Hamilton D . Bacteriophage P1 site-specific recombination. I. Recombination between loxP sites J Mol Biol 1981 150: 467–486

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  1. Gray Laboratory Cancer Research Trust, Mount Vernon Hospital, Northwood, HA6 2JR, Middlesex, UK

    S D Scott & B Marples

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  1. S D Scott
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  2. B Marples
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Scott, S., Marples, B. Comment on the use of the cre/loxP recombinase system for gene therapy vectors. Gene Ther 7, 1706 (2000). https://doi.org/10.1038/sj.gt.3301305

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