Ultrasound-assisted nonviral gene transfer of AQP1 to the irradiated minipig parotid gland restores fluid secretion

Z. Wang, L. Zourelias, C. Wu, Paul Edwards, M. Trombetta, M. J. Passineau

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Xerostomia is a common side effect of ionizing radiation used to treat head and neck cancer. A groundbreaking Phase I human clinical trial using Adenoviral gene transfer of Aquaporin-1 (AQP1) to a single salivary gland of individuals suffering from radiation-induced xerostomia has recently been reported. Unfortunately, the limitations of the Adenoviral vector system used in this pioneering trial preclude its advancement to a Phase II trial, and we have thus undertaken to evaluate the therapeutic potential of ultrasound-assisted nonviral gene transfer (UAGT) as an alternative means of delivering AQP1 gene therapy to the salivary gland by comparing head-to-head with the canonical Adenoviral vector in a swine model. Swine irradiated unilaterally with a 10-Gy electron beam targeted at the parotid gland suffered from significant, sustained hyposalivation that was bilateral, despite irradiation being confined to the targeted gland. Unilateral AQP1 gene therapy with UAGT resulted in bilateral restoration of stimulated salivary flow at 48 h and 1 week post treatment (1.62±0.48 ml and 1.87±0.45 ml) to preinjury levels (1.34±0.14 ml) in a manner comparable to Adenoviral delivery (2.32±0.6 ml and 1.33±0.97 ml). UAGT can replace the Adenoviral vector as a means of delivering AQP1 gene therapy in the irradiated swine model, and it is a candidate for advancement to a Phase I human clinical trial.

Original languageEnglish (US)
Pages (from-to)739-749
Number of pages11
JournalGene Therapy
Volume22
Issue number9
DOIs
StatePublished - Sep 5 2015

Fingerprint

Aquaporin 1
Miniature Swine
Fluids and Secretions
Parotid Gland
Xerostomia
Genetic Therapy
Clinical Trials, Phase I
Swine
Salivary Glands
Genes
Head and Neck Neoplasms
Ionizing Radiation
Electrons
Radiation
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Ultrasound-assisted nonviral gene transfer of AQP1 to the irradiated minipig parotid gland restores fluid secretion. / Wang, Z.; Zourelias, L.; Wu, C.; Edwards, Paul; Trombetta, M.; Passineau, M. J.

In: Gene Therapy, Vol. 22, No. 9, 05.09.2015, p. 739-749.

Research output: Contribution to journalArticle

Wang, Z. ; Zourelias, L. ; Wu, C. ; Edwards, Paul ; Trombetta, M. ; Passineau, M. J. / Ultrasound-assisted nonviral gene transfer of AQP1 to the irradiated minipig parotid gland restores fluid secretion. In: Gene Therapy. 2015 ; Vol. 22, No. 9. pp. 739-749.
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