ArticleMolecular therapy. Methods & clinical development2020
Transduction of Salivary Gland Acinar Cells with a Novel AAV Vector 44.9.
Article in Molecular therapy. Methods & clinical development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Advances in Gene Therapy for Xerostomia: Current Perspectives and Future Directions: A Narrative Review.Health science reports · 2026Article
- Terminal glucose as a receptor for adeno-associated virus 44.9.Journal of virology · 2026Article
- Amplified Type I Interferon Response in Sjögren's Disease via Ectopic Toll-Like Receptor 7 Expression in Salivary Gland Epithelial Cells Induced by Lysosome-Associated Membrane Protein 3.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- Systemic gene therapy using an AAV44.9 vector rescues a neonatal lethal mouse model of propionic acidemia.Molecular therapy. Methods & clinical development · 2023Article
- Gene Therapeutic Delivery to the Salivary Glands.Advances in experimental medicine and biology · 2023Article
- Systemic gene therapy for methylmalonic acidemia using the novel adeno-associated viral vector 44.9.Molecular therapy. Methods & clinical development · 2022Article
- Salivary gland function, development, and regeneration.Physiological reviews · 2022Review
- β-Adrenergic signaling induces Notch-mediated salivary gland progenitor cell control.Stem cell reports · 2021Article
- Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
The loss of salivary gland function caused by radiation therapy of the head and neck or autoimmune disease such as Sjögren's syndrome is a serious condition that affects a patient's quality of life. Due to the combined exocrine and endocrine functions of the salivary gland, gene transfer to the salivary glands holds the potential for developing therapies for disorders of the salivary gland and the expression of therapeutic proteins via the exocrine pathway to the mouth, upper gastrointestinal tract, or endocrine pathway, systemically, into the blood. Recent clinical success with viral vector-mediated gene transfer for the treatment of irradiation-induced damage to the salivary glands has highlighted the need for the development of novel vectors with acinar cell tropism able to result in stable long-term transduction. Previous studies with adeno-associated virus (AAV) focused on the submandibular gland and reported mostly ductal cell transduction. In this study, we have screened AAV vectors for acinar cell tropism in the parotid gland utilizing membrane-tomato floxed membrane-GFP transgenic mice to screen CRE recombinase encoding AAV vectors of different clades to rapidly identify capsid isolates able to transduce salivary gland acinar cells. We determined that AAVRh10 and a novel isolate found as a contaminant of a laboratory stock of simian adenovirus SV15, AAV44.9, are both able to transduce parotid and sublingual acinar cells. Persistence and localization of transduction of these AAVs were tested using vectors encoding firefly luciferase, which was detected 6 months after vector administration. Most luciferase expression was localized to the salivary gland compared to that of distal organs. Transduction resulted in robust secretion of recombinant protein in both blood and saliva. Transduction was species specific, with AAVRh10 having stronger transduction activity in rats compared with AAV44.9 or AAV2 but weaker in human primary salivary gland cells. This work demonstrates efficient transduction of parotid acinar cells by AAV that resulted in secretion of recombinant protein in both serum and saliva.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.