Effect of serotype 5 adenoviral and serotype 2 adeno- associated viral vector-mediated gene transfer to salivary glands on the composition of saliva.
Key to the development of a useful clinical therapy is the minimization of side effects. Routine safety testing, however, does not provide information about the physiological status of many potentially useful gene transfer target sites. In this study, we evaluated the longitudinal effects of intrasalivary duct delivery of recombinant serotype 5 adenoviral (rAd5; 10(9)-10(10) particles/gland in rats) and recombinant serotype 2 adeno-associated viral (rAAV2; 10(8)-10(9) particles/gland in mice) vectors on salivary composition. Both vectors led to modest, transient alterations in several salivary components that thereafter returned to normal. The changes suggested two initial specific consequences of rAd5 and rAAV2 vector administration: (1) a modest breach of the mucosal barrier in the targeted glands, indicated by elevations in salivary albumin, total protein, and Na+ levels, and (2) an innate host response, indicated by transient elevations in either salivary lactoferrin and IgA levels (rAd5) or mucin (rAAV2). These studies are consistent with the notion that administration of modest doses of rAd5 and rAAV2 vectors to salivary glands for a therapeutic purpose can be accomplished without severe or permanent injury to the target tissue, or compromise to its essential exocrine physiological function.
Wang
Jianghua
J
Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, DHHS, Bethesda, MD 20892-1190, USA.
Voutetakis
Antonis
A
Mineshiba
Fumi
F
Illei
Gabor G
GG
Dang
Howard
H
Yeh
Chih-Ko
CK
Baum
Bruce J
BJ
D000256:Adenoviridae; D000418:Albumins / Q000378:metabolism; D000818:Animals; D000229:Dependovirus; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors / Q000009:adverse effects; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism; D051379:Mice; D009077:Mucins / Q000378:metabolism; D051381:Rats; D011995:Recombination, Genetic; D012463:Saliva / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D014161:Transduction, Genetic
D000418:Albumins; D007074:Immunoglobulin G; D009077:Mucins; D012964:Sodium; D007781:Lactoferrin