Considerable progress has occurred recently in transferring foreign genes to different tissues in vivo. Gene transfer to salivary glands has mirrored progress in the general field. Most salivary studies have utilized replication-deficient, recombinant adenoviruses as gene transfer vectors in rat models. These vectors are able to transduce almost all rat salivary epithelial cell types and lead to relatively high levels of transgene expression. Additionally, successful, though quite modest, gene transfer to salivary glands has been achieved with retroviral vectors and with different plasmid conjugates (liposomes; non-recombinant adenoviruses). Salivary gland gene transfer has been used for two potential clinical goals: (i) the repair of hypo-functional gland parenchyma, and (ii) the production of secretory transgene products for either systemic or upper gastrointestinal tract pharmaceutical use. Gene transfer can also be used as a powerful tool to alter cellular phenotype in vivo and probe cell biological questions. The current spectrum of studies demonstrates the potential broad and profound influence gene transfer can make on salivary physiology and pathophysiology.
References
1.
Adesanya MR, Redman RS, Baum BJ, O'Connell BC (1996). Immediate inflammatory responses to adenovirus-mediated gene transfer in rat salivary glands. Hum Gene Ther7:1085-1093.
2.
Azen EA, Leutenegger W., Peters EH (1978). Evolutionary and dietary aspects of salivary basic (Pb) and post Pb (PPb) proteins in anthropod primates. Nature273:775-778.
3.
Barka T., van der Noen HM (1996). Retrovirus-mediated gene transfer into salivary glands in vivo. Hum Gene Ther7:613-618.
4.
Barka T., van der Noen HM (1997). Retrovirus-mediated gene transfer into rat salivary gland cells in vitro and in vivo. J Histochem Cytochem45:1533-1545.
5.
Becker TC, Noel RJ, Coats WS, Gomez-Foix AM, Alam T., Gerard RD, et al. (1994). Use of recombinant adenovirus for metabolic engineering of mammalian cells. Meth Cell Biol43:161-189.
6.
Bergelson JM, Cunningham JA, Droguett G., Kurt-Jones EA, Krithivas A., Hong JS, et al. (1997). Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5. Science275:1320-1323.
7.
Bramson JL, Graham FL, Gauldie J. (1995). The use of adenoviral vectors for gene therapy and gene transfer in vivo. Curr Opin Biotechnol6:590-595.
8.
Castle D., Castle A. (1998). Intracellular transport and secretion of salivary proteins. Crit Rev Oral Biol Med9:4-22.
9.
Chao J., Chao L. ( 1996). Functional analysis of human tissue kallikrein in transgenic mouse models. Hypertension27:491-494.
10.
Cooper LF, Elia DM, Tabak LA (1991). Secretagogue-coupled changes in the expression of glutamine/glutamic acid-rich proteins (GRPs). Isoproterenol induces changes in GRP transcript expression and changes in isoforms secreted. J Biol Chem266:3532-3539.
11.
Crystal RG (1995). Transfer of genes to humans: early lessons and obstacles to success. Science270:404-410.
12.
Delporte C., O'Connell BC, He X., Lancaster HE, O'Connell AC, Agre P., et al. (1997a). Increased fluid secretion after adenoviral-mediated transfer of the aquaporin- 1 cDNA to irradiated rat salivary glands. Proc Natl Acad Sci USA94:3268-3273.
13.
Delporte C., Redman RS, Baum BJ ( 1997b). Relationship between the cellular distribution of the αvβ3/5 integrins and adenoviral infection in salivary glands. Lab Invest77:167-173.
14.
Delporte C., Miller G., Kagami H., Lillibridge CD, O'Connell BC, Atkinson JC, et al. (1998). Safety of salivary gland administered, replication-deficient recombinant adenovirus in rats. J Oral Pathol Med27:34-38.
15.
Garrett JR, Chao J., Proctor GB, Wang C., Zheng XS, Chan K-M., et al. (1995). Influences of secretory activities in rat submandibular glands on tissue kallikrein circulating in the blood. Exp Physiol80:429-440.
16.
Goldfine ID, German MS, Tseng H-C., Wang J., Bolaffi JL, Chen J-W., et al. (1997). The endocrine secretion of human insulin and growth hormone by exocrine glands of the gastrointestinal tract. Nature Biotechnol15:1378-1382.
17.
He X., Goldsmith CM, Marmary Y., Wellner RB, Parlow AF, Nieman LK, et al. (1998). Systemic action of human growth hormone following adenovirus-mediated gene transfer to rat submandibular glands. Gene Ther5:537-541.
18.
Horowitz MS (1990). Adenoviridiae and their replication. In: Virology. Fields BN, Knipe DM, editors. New York: Raven Press, pp. 1679-1790.
19.
Isenman LD, Rothman SS (1977). Transport of a-amylase across the basolateral membrane of the pancreatic acinar cell. Proc Natl Acad Sci USA74:4068-4072.
20.
Jorgensen JOL (1991). Human growth hormone replacement therapy: pharmacological and clinical aspects. Endocrine Rev12:189-207.
21.
Kagami H., O'Connell BC, Baum BJ ( 1996). Evidence for the systemic delivery of a transgene product from salivary glands. Hum Gene Ther7:2177-2184.
22.
Kagami H., Atkinson JC, Michalek SM, Handelman B., Yu S., Baum BJ, et al. (1998). Repetitive adenovirus administration to the parotid gland: role of immunological barriers and induction of oral tolerance. Hum Gene Ther9:305-313.
23.
Kaplan MD, Baum BJ ( 1993). The functions of saliva. Dysphagia8:225-229.
24.
Kashima HK, Kirkham WR, Andrews JR (1965). Postradiation sialadenitis. A study of the clinical features, histopathologic changes and serum enzyme variations following irradiation of human salivary glands. Am J Roentgenol Radium Ther Nucl Med94:271-291.
25.
Lal K., Pollock JJ, Santarpia RPD, Heller HM, Kaufman HW, Fuhrer J., et al. (1992). Pilot study comparing the salivary cationic protein concentrations in healthy adults and AIDS patients: correlation with antifungal activity. J Acquir Immune Defic Syndr5:904-914.
26.
Laursen J., Hjorth JP (1997). A cassette for high-level expression in the mouse salivary glands. Gene198:367-372.
27.
Lillibridge CD, O'Connell BC (1997). In human salivary cells, overexpression of E2F1 overcomes an interferon-γ and tumor necrosis factor-a induced growth arrest but does not result in complete mitosis. J Cell Physiol172:343-350.
28.
Lin HH, Tu ZJ, Ann DK (1996). Involvement of nuclear orphan receptor NGFI-B in transcriptional activation of salivary-specific R15 gene by cAMP. J Biol Chem271:27637-27644.
29.
Mandel ID (1989). The role of saliva in maintaining oral homeostasis. J Am Dent Assoc119:298-304.
30.
Mastrangeli A., O'Connell B., Aladib W., Fox PC, Baum BJ, Crystal RG (1994). Direct in vivo adenovirus-mediated gene transfer to salivary glands. Am J Physiol266:G1146-G1155.
31.
Mulligan RC (1993). The basic science of gene therapy. Science260:926-932.
32.
O'Connell BC, Ten Hagen KG, Lazowski KW, Tabak LA, Baum BJ ( 1995). Facilitated DNA transfer to rat submandibular gland in vivo and GRP-Ca gene regulation. Am J Physiol268:G1074-G1078.
33.
O'Connell BC, Xu T., Walsh TJ, Sein T., Mastrangeli A., Crystal RG, et al. (1996). Transfer of a gene encoding the anticandidal protein histatin 3 to salivary glands. Hum Gene Ther7:2255-2261.
34.
Ting-C-N, Rosenberg MP, Snow CM, Samuelson LC, Meisler MH (1992). Endogenous retroviral sequences are required for tissue-specific expression of a human salivary amylase gene. Genes Dev6:1457-1465.
35.
Verma IM, Somia N. (1997). Gene therapy-promises, problems and prospects. Nature389:239-242.
36.
Wang C., Chao C., Chao L., Chao J. ( 1997). Expression of human tissue kallikrein in rat salivary glands and its secretion into circulation following adenovirus-mediated gene transfer. Immunopharm36:221-227.
37.
Wickham TJ, Mathias P., Cheresh DA, Nemerow GR (1993). Intergins αvβ3 and αvβ5 promote adenovirus internalization but not virus attachment. Cell73:309-319.
