Advances in salivary gland gene therapy – oral and systemic implications

Abstract

Introduction: Much research demonstrates the feasibility and efficacy of gene transfer to salivary glands. Recently, the first clinical trial targeting a salivary gland was completed, yielding positive safety and efficacy results.

Areas covered: There are two major disorders affecting salivary glands: radiation damage following treatment for head and neck cancers and Sjögren’s syndrome (SS). Salivary gland gene transfer has also been employed in preclinical studies using transgenic secretory proteins for exocrine (upper gastrointestinal tract) and endocrine (systemic) applications.

Expert opinion: Salivary gland gene transfer is safe and can be beneficial in humans. Applications to treat and prevent radiation damage show considerable promise. A first-in-human clinical trial for the former was recently successfully completed. Studies on SS suffer from an inadequate understanding of its etiology. Proof of concept in animal models has been shown for exocrine and endocrine disorders. Currently, the most promising exocrine application is for the management of obesity. Endocrine applications are limited, as it is currently impossible to predict if systemically required transgenic proteins will be efficiently secreted into the bloodstream. This results from not understanding how secretory proteins are sorted. Future studies will likely employ ultrasound-assisted and pseudotyped adeno-associated viral vector-mediated gene transfer.

Keywords:

• gene therapy
• non-viral gene transfer
• radiation damage
• salivary glands
• secretory proteins
• Sjögren’s syndrome
• viral vectors

Declaration of interest

I Alevizos has collaborative agreements with MedImmune, LLC for Sjögren’s syndrome-related studies. The authors are sincerely grateful to the Intramural Research Program of the National Institute of Dental and Craniofacial Research, NIH for the sustained support of their research on gene therapy with salivary glands. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Notes

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