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Suppression of Nonsense Mutations in the Dystrophin Gene by a Suppressor tRNA Gene

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Abstract

Nonsense mutations in the dystrophin gene are the cause of Duchenne muscular dystrophy (DMD) in 10–15% of patients. In such an event, one approach to gene therapy for DMD is the use of suppressor tRNAs to overcome the premature termination of translation of the mutant mRNA. We have carried out cotransfection of the HeLa cell culture with constructs containing a suptRNA gene (pcDNA3suptRNA) and a marker LacZ gene (pNTLacZhis) using their polymer VSST-525 complexes. It was found that the number of cells producing β-galactosidase depends inversely on the dose of the suptRNA gene. A single in vivo injection of the construct providing for expression of the suptRNAochre gene into mdx mouse muscle resulted in the production of dystrophin in 2.5% of fibers. This suggests that suppressor tRNAs are applicable in gene therapy for hereditary diseases caused by nonsense mutations.

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Authors and Affiliations

  1. Ott Institute of Obsterics and Gynecology, Russian Academy of Medical Sciences, St. Petersburg, 199034, Russia

    A. V. Kiselev, O. V. Ostapenko, A. N. Baranov, E. A. Lesina, T. E. Ivashchenko, V. A. Sabetskii & V. S. Baranov

  2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia

    E. V. Rogozhkina, N. S. Kholod, A. S. Seit-Nebi, V. O. Rechinsky & L. L. Kisselev

  3. Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, 197376, Russia

    M. M. Shavlovskii

Authors
  1. A. V. Kiselev
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  2. O. V. Ostapenko
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  3. E. V. Rogozhkina
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  4. N. S. Kholod
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  5. A. S. Seit-Nebi
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  6. A. N. Baranov
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  7. E. A. Lesina
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  8. T. E. Ivashchenko
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  9. V. A. Sabetskii
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  10. M. M. Shavlovskii
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  11. V. O. Rechinsky
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  12. L. L. Kisselev
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  13. V. S. Baranov
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Kiselev, A.V., Ostapenko, O.V., Rogozhkina, E.V. et al. Suppression of Nonsense Mutations in the Dystrophin Gene by a Suppressor tRNA Gene. Molecular Biology 36, 30–33 (2002). https://doi.org/10.1023/A:1014238221426

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  • DOI: https://doi.org/10.1023/A:1014238221426

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