ArticleProceedings of the National Academy of Sciences of the United States of America2004
Reengineered salivary glands are stable endogenous bioreactors for systemic gene therapeutics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 93 citations in OpenAlex.
- Development of a gene transfer-based treatment for radiation-induced salivary hypofunction.Oral oncology · 2010Trial
- USP18-mediated protein stabilization of NOTCH1 is associated with altered Th17/Treg cell ratios and B cell-mediated autoantibody secretion in Sjögren syndrome.Immunologic research · 2024Article
- Gene Therapeutic Delivery to the Salivary Glands.Advances in experimental medicine and biology · 2023Article
- Correction of LAMP3-associated salivary gland hypofunction by aquaporin gene therapy.Scientific reports · 2022Article
- CERE-120 Prevents Irradiation-Induced Hypofunction and Restores Immune Homeostasis in Porcine Salivary Glands.Molecular therapy. Methods & clinical development · 2020Article
- Delivery of human erythropoietin gene with an adeno-associated virus vector through parotid glands to treat renal anaemia in a swine model.Gene therapy · 2017Article
- In vivo tissue-tropism of adeno-associated viral vectors.Current opinion in virology · 2016Review
- Retroductal Submandibular Gland Instillation and Localized Fractionated Irradiation in a Rat Model of Salivary Hypofunction.Journal of visualized experiments : JoVE · 2016Article
- Advances in salivary gland gene therapy - oral and systemic implications.Expert opinion on biological therapy · 2015Review
- Gene therapy.Oral diseases · 2014Article
- Recombinant AAV9-TLK1B administration ameliorates fractionated radiation-induced xerostomia.Human gene therapy · 2013Article
- Article
- Gene therapy using IL-27 ameliorates Sjögren's syndrome-like autoimmune exocrinopathy.Arthritis research & therapy · 2012Article
- Including the p53 ELAV-like protein-binding site in vector cassettes enhances transgene expression in rat submandibular gland.Oral diseases · 2012Article
- A novel hybrid adenoretroviral vector with more extensive E3 deletion extends transgene expression in submandibular glands.Human gene therapy methods · 2012Article
- TACI-Fc gene therapy improves autoimmune sialadenitis but not salivary gland function in non-obese diabetic mice.Oral diseases · 2012Article
- An AAV2/5 vector enhances safety of gene transfer to the mouse salivary gland.Journal of dental research · 2012Article
- Local delivery of AAV2-CTLA4IgG decreases sialadenitis and improves gland function in the C57BL/6.NOD-Aec1Aec2 mouse model of Sjögren's syndrome.Arthritis research & therapy · 2012Article
- Article
- Gene delivery in salivary glands: from the bench to the clinic.Biochimica et biophysica acta · 2011Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The use of critical-for-life organs (e.g., liver or lung) for systemic gene therapeutics can lead to serious safety concerns. To circumvent such issues, we have considered salivary glands (SGs) as an alternative gene therapeutics target tissue. Given the high secretory abilities of SGs, we hypothesized that administration of low doses of recombinant adeno-associated virus (AAV) vectors would allow for therapeutic levels of transgene-encoded secretory proteins in the bloodstream. We administered 10(9) particles of an AAV vector encoding human erythropoietin (hEPO) directly to individual mouse submandibular SGs. Serum hEPO reached maximum levels 8-12 weeks after gene delivery and remained relatively stable for 54 weeks (longest time studied). Hematocrit levels were similarly increased. Moreover, these effects proved to be vector dose-dependent, and even a dosage as low as 10(8) particles per animal led to significant increases in hEPO and hematocrit levels. Vector DNA was detected only within the targeted SGs, and levels of AAV copies within SGs were highly correlated with serum hEPO levels (r = 0.98). These results show that SGs appear to be promising targets with potential clinical applicability for systemic gene therapeutics.
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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.