New findings from University of Minnesota in the area of molecular therapies published
2007 SEP 6 -- "The Sleeping Beauty (SB) transposon system mediates chromosomal integration and stable gene expression when an engineered SB transposon is delivered along with transposase. One concern in the therapeutic application of the SB system is that persistent expression of transposase could result in transposon instability and genotoxicity," scientists in the United States report. "Here, we tested the use of transposase-encoding RNA plus transposon DNA for correction of murine fumarylacetoacetate hydrolase (FAH) deficiency. A bi-functional transposon containing both mouse FAH and firefly luciferase sequences was used to track the growth of genetically corrected liver tissue by in vivo bioluminescence imaging after delivery of DNA or RNA as a source of transposase. Supplying SB transposase in the form of RNA resulted in selective repopulation of corrected hepatocytes with stable expression of FAH and luciferase. Plasma succinylacetone and amino acid levels were normalized, suggesting normal liver metabolism of catabolized protein products. Secondary FAH-deficient animals transplanted with hepatocytes (250,000) isolated from primary treated animals survived 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione (NTBC) withdrawal, gained weight consistently, and demonstrated stable expression of luciferase," wrote A. Wilber and colleagues, University of Minnesota. The researchers concluded: "We conclude that transposase-encoding messenger RNA (mRNA) can be used to mediate stable non-viral gene therapy, resulting in complete phenotypic correction, and is thus an effective source of recombinase activity for use in human gene therapy." Wilber and colleagues published their study in Molecular Therapy (Messenger RNA as a source of transposase for Sleeping Beauty transposon-mediated correction of hereditary tyrosinemia type I. Molecular Therapy, 2007;15(7):1280-1287). For additional information, contact X. Wang, University of Minnesota, Stem Cell Institute, Dept. of Laboratory Med & Pathology, 2-224 McGuire Translat Research Facil, 2001 6th St. SE, Minneapolis, MN 55455, USA. The publisher's contact information for the journal Molecular Therapy is: Nature Publishing Group, 75 Varick Street, 9TH Floor, New York, NY 10013-1917, USA. Keywords: United States, Minneapolis, Biotechnology, DNA, Enzymology, Gene Therapy, Genetics, Genomics, Molecular Research, Molecular Therapies, Nanotechnology, Protein Design, Protein Engineering, Proteomics, Transposase, Tyrosinemia, University of Minnesota. This article was prepared by Genetics & Environmental Business Week editors from staff and other reports. Copyright 2007, Genetics & Environmental Business Week via NewsRx.com.
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