Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability to target specific tissues is important in many applications of gene therapy. In this respect, a disadvantage of adenoviral vectors is the relative lack of specificity with which they transduce cells. One approach to overcome this is to express the therapeutic gene under the control of a tissue-specific promoter. However, the specificity and activity of these promoters may be altered by adenoviral sequences in the vector backbone. In contrast, helper-dependent adenoviral (HDAd) vectors [Parks, R.J., Chen, L., Anton, M., Sankar, U., Rudnicki, M.A., and Graham, F.L. (1996). Proc. Natl. Acad. Sci. U.S.A. 93, 13565-13570] are almost completely devoid of adenovirus sequences, and this may preserve the specificity of these heterologous promoters. We have compared HDAd and first-generation adenoviral (FGAd) vectors with respect to tissue-specific expression from prostate-specific antigen (PSA) or tyrosinase promoters/enhancers. A PSA-positive cell line (LNCaP) and a panel of PSA-negative cell lines were infected with HDAd vectors expressing luciferase under the control of three different kinds of PSA promoter/enhancer constructs. The results showed that these PSA promoter/enhancer cassettes in HDAd vectors maintained strict tissue-specific expression, but lost specificity when expressed from FGAd vectors. Similar results were observed with tyrosinase promoter-carrying vectors, except that the tyrosinase promoter retained a small degree of tissue specificity in FGAd vectors. Insertion of a murine cytomegalovirus immediate-early gene promoter-beta-galactosidase (MCMV-lacZ)-expressing cassette into a second site in the HDAd vector backbone significantly impaired the tissue specificity of the PSA and tyrosinase promoters. These results indicate that HDAd vectors are superior to FGAd vectors in their ability to maintain high levels of tissue-specific expression from PSA and tyrosinase promoters/enhancers. They also suggest that tissue-specific expression can be influenced not only by Ad sequences, but also by other viral and/or strong constitutive promoter/enhancers (such as the MCMV promoter) in the vector backbone.
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PMID:Superior tissue-specific expression from tyrosinase and prostate-specific antigen promoters/enhancers in helper-dependent compared with first-generation adenoviral vectors. 1181 78

Adenovirus vectors are the most highly efficient vehicles currently available for gene transfer to mammalian cells. Their ability to transduce both proliferating and non-dividing cells allows in vivo gene delivery, but the wide spectrum of cell types infected by adenovirus necessitates a requirement for targeting, particularly if the transduced gene is detrimental when expressed in inappropriate tissues. Over the past decade, numerous investigators have examined tissue- or tumor-specific enhancer-promoters as a means to transcriptionally target genes delivered by adenovirus vectors. We review here recent developments in adenovirus vectors including improvements in the vector backbone to maintain promoter specificity. In addition, we discuss the regulatory elements directing cell-specific expression of genes encoding telomerase, prostate-specific antigen, probasin, osteocalcin, tyrosinase, alpha-fetoprotein, surfactant B, and mammaglobin. Recent results using these regulatory sequences to target Ad vectors to cancer cells are highlighted.
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PMID:Transcriptionally targeted adenovirus vectors. 1610 15