Chercheurs

Médecine / KMIEC, ERIC B.

ekmiec

Position

Molecular biologist,

Professor,
Delaware Biotechnology Institute
Delaware Technology Park
University of Delaware,
Newark, USA.

Thèmes de recherche

- Mechanism of oligonucleotide-directed gene repair - Using a genetic readout system and cell free extracts from human and plant cells, the molecular and biochemical events underlying gene repair are being studied in yeast, bacteria and mammalian cells.

- Development of DNA base therapeutics for Huntington's Disease - A cell-based assay system is being employed to explore ways to prevent the aggregation activity of the Huntington protein.
Gene therapy for inherited disorders - Primary patient cells are being used to test the efficacy of gene editing for Hemophilia B, Spinal Muscular Atrophy (SMA), Muscular Dystrophy (MD) and Phenylketonuria (PKU).

- Targeted mutagenesis in mouse embryonic stem cells - New method for the creation of genetic mutations in mice using single-stranded oligonucleotides is being developed.

- Collaborative cancer research - Introduction of oligonucleotides to increase the sensitivity of cancer cells to treatment.

Prix et récompenses

Publications

Drury M and Kmiec EB (2005). A tolerance of DNA heterology in the mammalian targeted gene repair reaction. Oligonucleotides (in press).

Parekh-Olmedo, Ferrara L, and Kmiec EB (2005). Progress and Prospects: targeted gene repair. Gene Therapy 12, 639-646.

Brachman E and Kmiec EB (2005). Gene repair in mammalian cells is stimulated by the elongation of S phase and transient stalling of replication forks. DNA Repair 4, 445-457.

Hu Y, Parekh-Olmedo H, Drury M, Skogen M, and Kmiec EB (2005). Reaction parameters of targeted gene repair in mammalian cells. Molecular Biotechnology 29, 197-210.

Drury M and Kmiec EB (2004). Double displacement loops (double d-loops) are a more active template for gene repair activity. Oligonucleotides 14, 4, 274-86.

Ferrara L and Kmiec EB (2004). Camptothecin enhances the frequency of oligonucleotide-directed gene repair in mammalian cells by inducing DNA damage and activating homologous recombination. Nucleic Acids Research 32, 17, 5239-5248.

Ferrara L, Parekh-Olmedo H, and Kmiec EB. DNA damage increases the frequency of gene repair in mammalian cells. Experimental Cell Research 300, 1, 170-179 (2004).

Brachman E and Kmiec EB (2004). DNA replication impacts repair frequency and transcription strand bias in targeted nucleotide exchange. J. Cell Science 117, 17, 3867-3874.

van Brabant A, Williams JK, Parekh-Olmedo H, and Kmiec EB (2004). Gene editing of a human gene in yeast artificial chromosomes using modified single-stranded DNA and dual targeting. The Pharmacogenomics Journal, 4, 175-183.

Liu L, Maguire KK, and Kmiec EB (2004). Engineering the eukaryotic recombinase Rad51 increases the frequency of gene repair in vivo. Nucleic Acids Research 32, 2093-2101.

Drury M and Kmiec EB (2003). DNA pairing is an important step in the process of targeted nucleotide exchange. Nucleic Acids Research 31, 3, 899-910.

Tran ND, Liu X, Yan Z, Abbote D, Jiang Q, Kmiec EB, Sigmund CD, and Engelhardt JF (2003). Efficiency of chimeraplast gene targeting by direct nuclear injection using a GFP recovery assay. Molecular Therapy 7, 2, 248-253.

Gamper HB, Nulf CJ, Corey DR, and Kmiec EB (2003). The synaptic complex of RecA protein participates in hybridization and inverse strand exchange reactions. Biochemistry 42, 2643-2655.

Brachman E and Kmiec EB (2003). Targeted nucleotide repair of cyc1 mutations in Saccharomyces cerevisiae directed by modified single-stranded DNA oligonucleotides. Genetics 163, 2, 527-538.

Kmiec EB (2003). Targeted gene repair - in the arena. Journal of Clinical Investigation 112, 5, 632-636.

Liu L, Hu Y, Usher M, and Kmiec EB (2003). The nuclease activity of Saccharomyces cerevisiae Mre11 functions in targeted nucleotide alteration. Applied and Environmental Microbiology 69, 10, 6216-6224.

Parekh-Olmedo H and Kmiec EB (2003). Targeted nucleotide exchange in the CAG repeat region of the human HD gene. Biochem. Biophys. Res. Com. 310, 2, 660-666.

Liu L, Parekh-Olmedo H, and Kmiec EB (2003). Development and regulation of gene repair. Nature Reviews Genetics 4, 679-689.

Parekh-Olmedo H, Engstrom J, and Kmiec EB (2003). The effect of hydroxyurea and trichostatin A on targeted nucleotide exchange in yeast and mammalian cells. New York Academy of Science 1002, 43-56.

Hu Y, Liu L, and Kmiec EB (2003). Reduction of Htt inclusion formation in strains of Saccharomyces cerevisiae deficient in certain DNA repair functions: A statistical analyses of phenotype. Experimental Cell Research 291, 1, 46-55.

Rice MC, Heckman B, Liu Y, and Kmiec EB (2003). Fluorescent detection and isolation of DNA variants using stabilized RecA-coated oligonucleotides. Genome Research 14, 116-125.

Maguire K and Kmiec EB (2003). Enhancement of in vivo targeted nucleotide exchange by nonspecific, carrier DNA. Methods in Molecular Biology 262, 13, 209-219.

Kmiec EB (2002). Toward the mechanism of chimera-directed gene repair. In: Encyclopedia of the Human Genome. Nature Publishing Group.

Parekh-Olmedo H, Krainc D, and Kmiec EB (2002). Targeted gene repair and its application to neurodegenerative disorders. Neuron 33, 495-49.

Liu H, Agarwal S, Kmiec EB, and Davis BR (2002). Targeted beta-globin gene conversion in human hematopoietic CD34(+) and Lin(-)CD38(-) cells. Gene Therapy 9, 118-126.

Liu L, Rice MC, Drury M, Cheng S, Gamper H, and Kmiec EB (2002). Strand bias in targeted gene repair is influenced by transcriptional activity. Molecular and Cellular Biology 22, 11, 3852-3863.

Brachman E and Kmiec EB (2002). The 'biased' evolution of targeted gene repair (review). Current Opinion in Molecular Therapeutics 4, 2, 171-176.

Liu L, Cheng S, van Brabant A, and Kmiec EB (2002). Rad51p and Rad54p, but not Rad52p, elevate gene repair in Saccharomyces cerevisiae directed by modified single-stranded oligonucleotide vectors. Nucleic Acids Research 30, 13, 2742-2750.

Parekh-Olmedo H, Drury M, and Kmiec EB (2002). Targeted nucleotide exchange in Saccharomyces cerevisiae directed by short oligonucleotides containing locked nucleic acids. Chem. Biol. 9, 1073-1084.

Agarwal S, Gamper HB, and Kmiec EB (2002). Multiple nucleotide replacement can be directed by modified single-stranded oligonucleotides in vitro and in vivo. Biomolecular Engineering 20, 1, 7-20.