{BLR 2517} AAV Vectors - American Biogenetic Sciences - Antex Biologies - Aptein, Inc. - ArQule - Atherosclerosis - Aurora Biosciences - BRCA Genes - Breast Cancer - Camplyobacter jejuni - CardioGene - Cell Genesys - Chimeric Antibodies - Chromagen, Inc. - Ciliary Neurotrophic Factor - Cyanoacrylates - Diabetes - Dyax - Elanex - Erythropoietin - Fluorescence - Gene Therapy - Genelabs - Genetic Vectors - Immunomedics - Integra - Interferons - Japan - Korea - Lark Technologies - Lucent Medical - MedLogic - Membrane Potential - Mortalin - Neutrophil Elastase - Nucleotide Probes - Nutriment Signal Transduction - Oncormed - Parkinson's Disease - PE Applied Biosystems - Polymers - Polysome Display - Regeneran Pharmaceuticals - Retinitis Pigmentosa - Retroviral Vectors - Shaman Pharmaceuticals - Telios - Thrombosis - Tissue Regeneration - Viragen

1997 ◽  
Vol 16 (5-6) ◽  
pp. 577-582
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Gene Therapy ◽  
Membrane Potential ◽  
Tissue Regeneration ◽  
Neurotrophic Factor ◽  
Retroviral Vectors ◽  
Ciliary Neurotrophic Factor ◽  
Chimeric Antibodies ◽  
Genetic Vectors

Profiling Retroviral Integration Sites in Donor T-Lymphocytes for Suicide Gene Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1744-1744
Author(s):  
Frank A. Giordano ◽  
Stephanie Laufs ◽  
Katalin Z. Nagy ◽  
Boris Fehse ◽  
Agnes Hotz-Wagenblatt ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Gene Therapy ◽  
T Cells ◽  
T Lymphocytes ◽  
Homo Sapiens ◽  
Severe Combined Immunodeficiency ◽  
Retroviral Vectors ◽  
Hematopoietic Stem ◽  
Retroviral Integration ◽  
Integration Sites

Abstract Retroviral vectors encoding the herpes simplex thymidine kinase gene (HSV-Tk) have been employed to render T-lymphocytes (TLCs) sensitive to the prodrug ganciclovir. Such genetically modified T cells have been used for adoptive immunotherapy in the context of allogeneic hematopoietic stem cell transplantation (SCT). Infused T cells have been shown to be susceptible to elimination through exposure to ganciclovir in the event of graft-versus-host disease (GvHD). Recent reports on insertional “genotoxicity” in a mouse gene marking study and a clinical gene therapy trial for X-chromosomal severe combined immunodeficiency (X-SCID) reminded us the actual risk of insertional oncogene activation and subsequent leukemia development. Here we investigated retroviral integration sites in donor TLCs transduced with the MoLV-based TK/neoR vector Mo3TIN of four donors in a clinical HSV-Tk study. A total of 114 retroviral integration sites were detected using highly sensitive and specific ligation-mediated PCR (LM-PCR). 41.2% of all integrations appeared near the transcription start regions (+/−10kb) of genes. Further analysis showed that 57 (50%) of all integrations targeted RefSeq genes. 24 of those appeared in intron 1 (42% of all integrations into genes) while 18% (10/57) of all integrations into genes landed in exon sequences whereas 6 hit the first exon. 18 of the targeted genes (15.8% of all integrations) could be at last assigned to signal transduction pathways, whereas the transcription factor family was afflicted 13 times (11.4% of all integrations). The zinc ion binding group makes up 4 (resp. 6, minding that GTF2HII contains a C2H2 type and KIAA0427 a C-x8-C-x5-C-x3-H-type zinc finger) of them. Among the targeted genes we found integrations into the CD8, CD100, CD44, CX3CR1, HLA-DMP and IL10-receptor genes. Within at a range of 5kb up- and 5kb downstream of vector integrations 15 genes were located that were not hit. 5 are known as transcription factors, whereas two of those are involved in leukemia, namely the homo sapiens myeloid/lymphoid or mixed-lineage leukemia 5 gene (MLL5) and the homo sapiens ALL1 fused gene from 5q31 (AF5Q31). Hit genes are currently examined more systematically in terms of function, e.g. involvement in signal transduction and transcription promoting processes. RISC (Retroviral Insertion estimate of Chromosomal Integration) scores and integration specific data will be submitted to a data warehouse, the collaborative RISC score database (CRSD). Such a systematic data collection similar to the IBMTR or EBMT databases will allow to recognize factors contributing to the safety, optimal transgene expression and persistence of transduced cells in the setting of allogenic matched donor transplantation.

scholarly journals Ciliary Neurotrophic Factor Induces Down-regulation of Its Receptor and Desensitization of Signal Transduction Pathwaysin Vivo

1996 ◽  
Vol 271 (37) ◽  
pp. 22839-22846 ◽  
Author(s):  
Peter S. DiStefano ◽  
Teri G. Boulton ◽  
Jennifer L. Stark ◽  
Yuan Zhu ◽  
Krystyna M. Adryan ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Neurotrophic Factor ◽  
Ciliary Neurotrophic Factor ◽  
Down Regulation

Preventing blindness in retinal disease: ciliary neurotrophic factor intraocular implants

2007 ◽  
Vol 42 (3) ◽  
pp. 399-402 ◽  
Author(s):  
Ian M. MacDonald ◽  
Yves Sauvé ◽  
Paul A. Sieving
Keyword(s):  
Neurotrophic Factor ◽  
Retinal Disease ◽  
Ciliary Neurotrophic Factor
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