Safety of a Single Administration of AAV2hAQP1, an Adeno-Associated Viral Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in People With Irradiation-Induced Parotid Salivary Hypofunction

Background: \- Radiation can cause the parotid salivary glands to make less saliva (dry mouth). This can cause problems like infections and tooth decay. Researchers hope a new drug can help people with dry mouth caused by radiation. Objectives: \- To examine the safety of AAV2hAQP1 gene therapy. To see if the drug increases saliva in people whose parotid glands have had radiation. Eligibility: \- People at least 18 years of age with a history of radiation therapy for head and neck cancer. Design: Participants will be screened in 2 visits with:

• medical history
• physical exam
• scans of the head, neck, and chest
• intravenous administration of glycopyrrolate to stop saliva
• saliva collections
• sialogram which is a procedure in which a substance is injected in the parotid gland and X-rays are taken.
• non-drug infusion
• a small piece of skin being taken 3-5-day hospital stay: Participants will receive the gene infusion. The AAV2hAQP1 will be in a solution in a syringe. It will be slowly pushed into the parotid gland through the parotid duct, an opening in the mouth near the second upper molar tooth. 10 outpatient visits over 3 years. These may include:
• repeats of selected screening tests, including saliva collection
• blood and urine tests
• oral and dental examinations
• head and neck exams, including the use of a thin scope to see the back of the throat
• questionnaires
• a small piece of parotid tissue being taken by either a small scope through the parotid duct or by a small needle guided by ultrasound
• scans of the head and neck. For some, contrast will be injected in a vein
• completion of a diary about how the participant feels between visits
• swabs of teeth and gums to assess the microbiome of the mouth