Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have determined the sequence of an 812-bp BamHI-EcoRI restriction fragment containing the 5' region of the human gene for PGK (3-phosphoglycerate kinase or ATP:3-phospho-D-glycerate 1-phosphotransferase; EC 2.7.2.3). The fragment contains 450 bp 5' to three start points for transcription (located by primer extension and S1 nuclease mapping), a leader sequence 85-94 bp long, the first exon of gene (65 bp), and part of the first intron. The promoter region is extremely G + C-rich, lacks a TATA box, and has an 8-bp direct repeat. A comparison of the promoter region for PGK with other promoters on the X-chromosome reveals homology with the promoter for HPRT, but not with the operator for factor IX.
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PMID:Sequence of the promoter region of the gene for human X-linked 3-phosphoglycerate kinase. 609 25

Integration-deficient lentiviral vectors (IDLVs) have been shown to transduce a wide spectrum of target cells and organs in vitro and in vivo and to maintain long-term transgene expression in nondividing cells. However, epigenetic silencing of episomal vector genomes reduces IDLV transgene expression levels and renders these safe vectors less efficient. In this article, we describe for the first time a complete correction of factor IX (FIX) deficiency in hemophilia B mice by IDLVs carrying a novel, highly potent human FIX cDNA. A 50-fold increase in human FIX cDNA potency was achieved by combining two mechanistically independent yet synergistic strategies: (i) optimization of the human FIX cDNA codon usage to increase human FIX protein production per vector genome and (ii) generation of a highly catalytic mutant human FIX protein in which the arginine residue at position 338 was substituted with leucine. The enhanced human FIX activity was not associated with liver damage or with the formation of human FIX-directed inhibitory antibodies and rendered IDLV-treated FIX-knockout mice resistant to a challenging tail-clipping assay. A novel S1 nuclease-based B1-quantitative polymerase chain reaction assay showed low levels of IDLV integration in mouse liver. Overall, this study demonstrates that IDLVs carrying an improved human FIX cDNA safely and efficiently cure hemophilia B in a mouse model.
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PMID:Integration-deficient lentiviral vectors expressing codon-optimized R338L human FIX restore normal hemostasis in Hemophilia B mice. 2394 13