Gene Therapy and Therapeutics Branch, National Institute of Dental Research, Building 10/1N113, 10 Center Drive, National Institutes of Health, Bethesda, Maryland 20892-1190
a Oral Pathology Research Laboratory, Veterans Administration Medical Center, Washington, DC 20422
Recent developments in gene transfer technology have expanded
the range of
in vivo experimentation and provided new insights
that might be applicable to the treatment of human diseases.
Somatic gene transfer may complement conventional transgenic
animal experiments by allowing for more restricted gene expression.
Salivary glands of rats are readily transduced
in vivo by adenovirus
vectors. This model has been used to demonstrate the effects
of transferring a water channel (aquaporin) gene to glands that
have been damaged by radiation. Submandibular glands that receive
the aquaporin vector increase the stimulated salivary flow close
to normal levels. The possible role of E2F1 in promoting cell
regeneration
in vivo was also explored. A vector expressing
E2F1 was capable of increasing DNA synthesis in rat salivary
glands, though complete mitosis was not observed. Future generations
of vectors must overcome current limitations of efficiency,
immunogenicity, and transient expression.
