BVL-1-like VL30 promoter sustains long-term expression in erythroid progenitor cells.
Congenital blood disorders are common and yet clinically challenging globin disorders. Gene therapy continues to serve as a potential therapeutic method to treat these disorders. While tremendous advances have been made in vivo, gene delivery protocols and vector prototypes still require optimization. Alternative cis-acting promoter elements derived from VL30 retroelements have been effective in expressing tissue-specific transgene expression in vivo in nonerythroid cells. VL30 promoter elements were isolated from ELM-I-1 erythroid progenitor cells upon erythropoietin (epo) treatment. These promoters were inserted into a VL30-derived expression vector and reintroduced into the ELM-I-1 cells. beta-Galactosidase reporter gene activity from the ELM 5 clone, a BVL-1-like VL30 promoter, was capable of expressing sustained levels of the transgene expression over a 16-week assay period. These findings delineate the potential utility of these retroelement promoters as transcriptionally active, erythroid-specific, long terminal repeat (LTR) components for current globin vector constructs.
Staplin
William R
WR
Department of Biomedical Sciences, Creighton University, Omaha, NE, USA.
Knezetic
Joseph A
JA
D000818:Animals; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics*; D007763:Lac Operon; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D051379:Mice; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D018626:Retroelements / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000096:biosynthesis
D011993:Recombinant Fusion Proteins; D018626:Retroelements; D004921:Erythropoietin; D001616:beta-Galactosidase