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Evaluation of promoters for driving efficient transgene expression in neonatal porcine islets
Author(s) -
Londrigan Sarah L.,
Brady Jamie L.,
Sutherland Robyn M.,
Hawthorne Wayne J.,
Thomas Helen E.,
Jhala Guarang,
Cowan Peter J.,
Kay Thomas W. H.,
O'Connell Philip J.,
Lew Andrew M.
Publication year - 2007
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2007.00376.x
Subject(s) - islet , xenotransplantation , promoter , biology , transplantation , transgene , pancreatic islets , genetic enhancement , context (archaeology) , microbiology and biotechnology , gene delivery , gene , gene expression , immunology , insulin , endocrinology , medicine , genetics , paleontology
There is considerable interest in the viral modification of insulin‐producing islets, including porcine islets, in the context of islet xenotransplantation to treat type 1 diabetes. Adenovirus (Adv) gene delivery offers the potential to modify pre‐transplant islets for enhanced survival. Modifications include transfer of cytoprotective molecules to ensure islet survival immediately post‐transplant, and molecules to dampen the immune system and prevent chronic islet graft rejection. In this study, we compared different promoters (three promiscuous and two tissue‐specific promoters) for their efficiency in driving gene expression in neonatal pig islet tissue after Adv delivery. We also compared the efficiency of these promoters in adult islets from mouse and human pancreata. We observed that the promiscuous cytomegalovirus promoter was the most potent, eliciting high luciferase expression in neonatal pig islets, as well as in human and mouse islets. In contrast, the mammalian EF1‐ α promoter educed comparatively intermediate gene expression. The mouse major histocompatibility complex class I promoter H‐2K b and the pancreatic‐specific promoters insulin and human pdx‐1 (area II) performed poorly in islets from all three species. This has important implications for the generation of modified neonatal pig islets for transplantation into humans.