Genetic Vectors

Publication Title: 
Oncogene

Normal human breast epithelial cells were transfected with expression vectors containing the p53 gene mutated at either codon 143, 175, 248 or 273, or by infection with a recombinant retroviral vector containing the p53 gene mutated at codons 143, 175, 248, or 273. The breast epithelial cells were monitored for extension of in vitro lifespan and immortalization. Expression of some, but not all, p53 mutants resulted in an extension of in vitro lifespan.

Author(s): 
Gollahon, L. S.
Shay, J. W.
Publication Title: 
Oncogene

Replicative senescence is thought to be a significant barrier to human tumorigenesis, which in human fibroblasts, and many other cell types, can be overcome experimentally by combined loss of function of p53 and Rb 'pathways'. To avoid the confounding pleiotropic effects of HPVE7 frequently used in such studies, here we have employed retroviral vectors over-expressing CDK4 or CDK6 as a more representative model of naturally-occurring mutations targeting the Rb pathway.

Author(s): 
Morris, Mark
Hepburn, Peter
Wynford-Thomas, David
Publication Title: 
International Journal of Oncology

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined.

Author(s): 
Ojima, Toshiyasu
Iwahashi, Makoto
Nakamura, Masaki
Matsuda, Kenji
Nakamori, Mikihito
Ueda, Kentaro
Naka, Teiji
Katsuda, Masahiro
Miyazawa, Motoki
Yamaue, Hiroki
Publication Title: 
Experimental & Molecular Medicine

Neural progenitor cells (NPs) have shown several promising benefits for the treatment of neurological disorders. To evaluate the therapeutic potential of human neural progenitor cells (hNPs) in amyotrophic lateral sclerosis (ALS), we transplanted hNPs or growth factor (GF)-expressing hNPs into the central nervous system (CNS) of mutant Cu/Zn superoxide dismutase (SOD1(G93A)) transgenic mice.

Author(s): 
Park, Sungju
Kim, Hyoung-Tae
Yun, Seokkwan
Kim, Il-Sun
Lee, Jiyoon
Lee, Il-Shin
Park, Kook In
Publication Title: 
Molecular Therapy: The Journal of the American Society of Gene Therapy

Methylmalonic acidemia (MMA) is an organic acidemia caused by deficient activity of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT). This disorder is associated with lethal metabolic instability and carries a poor prognosis for long-term survival. A murine model of MMA that replicates a severe clinical phenotype was used to examine the efficacy of recombinant adeno-associated virus (rAAV) serotype 8 gene therapy as a treatment for MMA.

Author(s): 
Chandler, Randy J.
Venditti, Charles P.
Publication Title: 
Methods in Molecular Biology (Clifton, N.J.)

Intrauterine gene therapy (IUGT) potentially enables the treatment and possible cure of monogenic -diseases that cause severe fetal damage. The main benefits of this approach will be the ability to correct the disorder before the onset of irreversible pathology and inducing central immune tolerance to the vector and transgene if treatment is instituted in early gestation.

Author(s): 
Mattar, Citra N.
Biswas, Arijit
Choolani, Mahesh
Chan, Jerry K. Y.
Publication Title: 
Journal of Neurochemistry

The human tyrosine hydroxylase (hTH) gene has a 42†bp evolutionarily conserved region designated (CR) II at -7.24†kb, which bears 93% homology to the region we earlier identified as containing the glucocorticoid response element, a 7†bp activator protein-1 (AP-1)-like motif in the rat TH gene. We cloned this hTH-CRII region upstream of minimal basal hTH promoter in luciferase (Luc) reporter vector, and tested glucocorticoid responsiveness in human cell lines.

Author(s): 
Sheela Rani, C. S.
Soto-Pina, Alexandra
Iacovitti, Lorraine
Strong, Randy
Publication Title: 
Cold Spring Harbor Symposia on Quantitative Biology

Telomeres are maintained by the ribonucleoprotein (RNP) enzyme telomerase, which replenishes telomeres through its unique mechanism of internal RNA-templated addition of telomeric DNA. Telomerase is active in most human cancers, typically because its core protein subunit, TERT, is up-regulated. Although the major known function of telomerase in cancer is to replenish telomeric DNA and maintain cell immortality, the regulation of the RNA component of telomerase is not well understood.

Author(s): 
Li, S.
Blackburn, E. H.
Publication Title: 
Cancer Research

The telomerase ribonucleoprotein is a promising target for cancer therapy, as it is highly active in many human malignancies. A novel telomerase targeting approach combines short interfering RNA (siRNA) knockdown of endogenous human telomerase RNA (hTer) with expression of a mutant-template hTer (MT-hTer). Such combination MT-hTer/siRNA constructs induce a rapid DNA damage response, telomere uncapping, and inhibition of cell proliferation in a variety of human cancer cell lines.

Author(s): 
Goldkorn, Amir
Blackburn, Elizabeth H.
Publication Title: 
Cell

We have constructed a linear yeast plasmid by joining fragments from the termini of Tetrahymena ribosomal DNA to a yeast vector. Structural features of the terminus region of the Tetrahymena rDNA plasmid maintained in the yeast linear plasmid include a set of specifically placed single-strand interruptions within the cluster of hexanucleotide (C4A2) repeat units. An artificially constructed hairpin terminus was unable to stabilize a linear plasmid in yeast.

Author(s): 
Szostak, J. W.
Blackburn, E. H.

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