In Vivo Gene Transfer To Salivary Glands

Baum, Bruce J.; O’Connell, Brian

doi:10.1177/10454411990100030201

Cited by 37 publications

(26 citation statements)

References 31 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Salivary glands offer an unusual, but potentially useful, target site for both local and systemic gene therapeutics (e.g., Goldfine et al, 1997;Baum and O'Connell, 1999;Hoque et al, 2001). For example, we established, by using recombinant adenoviral vectors, that gene transfer to salivary glands could lead to the augmentation of saliva with an antifungal polypeptide , as well as provide the delivery of biologically active growth hormone into the bloodstream (He et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Recombinant Adeno-Associated Virus Serotype 2 Vectors Mediate Stable Interleukin 10 Secretion from Salivary Glands into the Bloodstream

et al. 2002

View full text Add to dashboard Cite

We have constructed a recombinant adeno-associated virus serotype 2 vector encoding human interleukin 10 (rAAVhIL10). IL-10 is a potent antiinflammatory/immune cytokine, which has received growing attention for its therapeutic potential. Human IL-10 (hIL-10) production was virus dose dependent after in vitro infection of HSG cells, a human submandibular gland cell line. The vector-derived hIL-10 produced was biologically active, as the medium from rAAVhIL10-infected HSG cells caused a dose-dependent blockade of IL-12 secretion from spleen cells of IL-10 knockout mice challenged with heat-killed Brucella abortus. Administration of rAAVhIL10 (10(10) genomes per gland) to both mouse submandibular glands led to hIL-10 secretion into the bloodstream (approximately 1-5 pg/ml), that is, in an endocrine manner, which was stable for approximately 2 months. Salivary gland administration of rAAVhIL10 under experimental conditions was more efficacious than intravenous administration (approximately 0.5-0.7 pg/ml). Also, hIL-10 was readily secreted in vitro from organ cultures of minced submandibular glands infected with rAAVhIL10, 6 or 8 weeks earlier. Consistent with these results, hIL-10 mRNA was detected by reverse transcription-polymerase chain reaction in submandibular glands of mice infected with rAAVhIL10 but not from control mice. At these doses, little to no hIL-10 was detected in mouse saliva. Using a rAAV serotype 2 vector encoding beta-galactosidase, we observed that the primary parenchymal target cells were ductal. These findings represent the first report of rAAV use to target exocrine glands for systemic secretion of a therapeutic protein, and support the notion that rAAV serotype 2 vectors may be useful in salivary glands for local (periglandular) and systemic gene-based protein therapeutics.

show abstract

Section: Introductionmentioning

confidence: 99%

Recombinant Adeno-Associated Virus Serotype 2 Vectors Mediate Stable Interleukin 10 Secretion from Salivary Glands into the Bloodstream

et al. 2002

View full text Add to dashboard Cite

show abstract

“…A method of treating salivary gland functional deficiencies makes use of this gene therapy approach. The aim of this method is to drive existing non-secretory ductal epithelial cells into secretory cells capable of fluid movement, and success in animal models has been demonstrated [139,140].…”

Section: Next Generation Approaches For Periodontal Tissue Engineeringmentioning

confidence: 99%

Growth factor delivery for oral and periodontal tissue engineering

Kaigler

Cirelli

Giannobile

2006

Expert Opinion on Drug Delivery

168

153

View full text Add to dashboard Cite

The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. Growth factors are critical to the development, maturation, maintenance and repair of craniofacial tissues, as they establish an extracellular environment that is conducive to cell and tissue growth. Tissue-engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. These materials have been constructed into devices that can be used as vehicles for delivery of cells, growth factors and DNA. In this review, different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral-and tooth-supporting structures, namely the periodontium and alveolar bone.

show abstract

“…12 Although currently used adenoviral vectors are not considered ideal for long-term stable gene transfer in mammals, they are, at present, the most efficient means for transferring genes to salivary glands in vivo. 13 Despite the clinical promise shown by recombinant adenoviruses for gene transfer to the salivary glands, there are no published reports examining adenovirus administration to salivary or other exocrine glands in primates. The primary purpose of the present study was to examine the safety of a single administration of a recombinant adenovirus to irradiated and nonirradiated parotid glands of rhesus monkeys.…”

mentioning

confidence: 99%

Safety and efficacy of adenovirus-mediated transfer of the human aquaporin-1 cDNA to irradiated parotid glands of non-human primates

et al. 1999

View full text Add to dashboard Cite

This study evaluated the safety and efficacy of a single administration of a recombinant adenovirus encoding human aquaporin-1 (AdhAQP1) to the parotid glands of adult rhesus monkeys. In anticipation of possible clinical use of this virus to correct irradiation damage to salivary glands, AdhAQP1 was administered (at either 2 ϫ 10 9 or 1 ϫ 10 8 plaque-forming units/gland) intraductally to irradiated glands and to their contralateral nonirradiated glands. Radiation (single dose, 10 Gy) significantly reduced salivary flow in exposed glands. Virus administration resulted in gene transfer to irradiated and nonirradiated glands and was without untoward local (salivary) or systemic (sera chemistry, complete blood count) effects in all animals. However, the effect of AdhAQP1 administration varied and did not result in a consistent positive effect on salivary flow rates for all animals under these experimental conditions. We conclude that a single adenoviral-mediated gene transfer to primate salivary glands is well-tolerated, although its functional utility in enhancing fluid secretion from irradiated parotid glands is inconsistent.

show abstract

In Vivo Gene Transfer To Salivary Glands

Cited by 37 publications

References 31 publications

Recombinant Adeno-Associated Virus Serotype 2 Vectors Mediate Stable Interleukin 10 Secretion from Salivary Glands into the Bloodstream

Recombinant Adeno-Associated Virus Serotype 2 Vectors Mediate Stable Interleukin 10 Secretion from Salivary Glands into the Bloodstream

Growth factor delivery for oral and periodontal tissue engineering

Safety and efficacy of adenovirus-mediated transfer of the human aquaporin-1 cDNA to irradiated parotid glands of non-human primates

Contact Info

Product

Resources

About