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Somatic gene therapy for hypertension.

M I Phillips1

  • 1Department of Physiology, College of Medicine, University of Florida, Gainesville 32610-0274, USA. mip@phys.med.ufl.edu

Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas
|June 1, 2000
PubMed
Summary

Gene therapy offers a promising alternative to current hypertension treatments, providing long-lasting blood pressure control. Antisense oligodeoxynucleotides (AS-ODN) and viral vectors show potential for sustained antihypertensive effects with minimal side effects.

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Area of Science:

  • Cardiovascular Research
  • Molecular Medicine
  • Gene Therapy

Background:

  • Current hypertension drugs face challenges with patient compliance, cost, and short duration of action.
  • Gene therapy presents a novel approach for achieving sustained antihypertensive effects, potentially lasting weeks to years.

Purpose of the Study:

  • To evaluate the efficacy of gene therapy strategies, specifically antisense oligodeoxynucleotides (AS-ODN) and viral vectors, for treating hypertension.
  • To investigate the potential for long-term blood pressure regulation through targeted gene inhibition.

Main Methods:

  • Utilized antisense oligodeoxynucleotides (AS-ODN) targeting key genes like angiotensinogen (AGT) and angiotensin type 1 receptors (AT1-R).
  • Employed adeno-associated virus (AAV) vectors carrying antisense DNA constructs to inhibit vasoconstrictive genes.

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  • Tested therapeutic strategies in rat models (SHR, 2K-1C) and double transgenic mice with induced hypertension.

    • Main Results:

    • AS-ODN, particularly when delivered via liposomes, demonstrated effective hypertension reduction in rat models with effects lasting up to one month.
    • A single administration of AAV vectors carrying antisense DNA to AGT or AT1-R significantly reduced blood pressure and slowed hypertension development in SHR.
    • AAV-AT1-R-AS treatment normalized blood pressure for over six months in double transgenic mice with severe hypertension.

    Conclusions:

    • Antisense oligodeoxynucleotides (AS-ODN) are likely to be developed first as a drug-like treatment for hypertension due to their long-term effects.
    • Viral vector gene therapy holds potential for very prolonged blood pressure control, but requires further safety engineering.