Journal ArticleDOI
Colocalization of retrovirus and target cells on specific fibronectin fragments increases genetic transduction of mammalian cells.
Helmut Hanenberg,Xiang Li Xiao,Dagmar Dilloo,Kimikazu Hashino,Ikunoshin Kato,David R. Williams +5 more
TLDR
It is demonstrated that enhanced gene transfer into mammalian target cells is due to direct binding of retroviral particles to sequences within the fibronectin molecule.Abstract:
Hematopoietic cells are important targets for genetic modification with retroviral vectors. Attempts at human gene therapy of stem cells have achieved limited success partly because of low gene transfer efficiency. Chymotryptic fragments of the extracellular matrix molecule fibronectin used during infection have been shown to increase transduction of human hematopoietic progenitor cells. Here, we demonstrate that this enhanced gene transfer into mammalian target cells is due to direct binding of retroviral particles to sequences within the fibronectin molecule. Transduction of mammalian cells, including murine long-term repopulating hematopoietic cells, is greatly enhanced when cells are adherent to chimeric fragments containing these retroviral binding sequences. In addition, colocalization of retrovirus and target cells on fibronectin peptides allows targeted transduction of specific cell types by exploiting unique ligand/receptor interactions.read more
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Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease
Marina Cavazzana-Calvo,Hacein-Bey S,Geneviève de Saint Basile,Fabian Gross,Eric Yvon,Patrick Nusbaum,Françoise Selz,Christophe Hue,Stéphanie Certain,Jean-Laurent Casanova,Philippe Bousso,Françoise Le Deist,Alain Fischer +12 more
TL;DR: A gene therapy trial for SCID-X1 was initiated, based on the use of complementary DNA containing a defective gammac Moloney retrovirus-derived vector and ex vivo infection of CD34+ cells, which provided full correction of disease phenotype and clinical benefit.
Journal ArticleDOI
RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism
Ji Li,Ildiko Sarosi,Xiao-Qiang Yan,Sean Morony,Casey Capparelli,Hong-Lin Tan,Susan McCabe,Robin Elliott,Sheila Scully,Gwyneth Van,Stephen J. Kaufman,Shao-Chieh Juan,Yu Sun,John E. Tarpley,Laura Martín,Kathleen Christensen,James McCabe,Paul J. Kostenuik,Hailing Hsu,Frederick A. Fletcher,Colin R. Dunstan,David L. Lacey,William J. Boyle +22 more
TL;DR: Data indicate that RANK is the intrinsic cell surface determinant that mediates osteoprotegerin ligand effects on bone resorption and remodeling as well as the physiological and pathological effects of calciotropic hormones and proresorptive cytokines.
Journal ArticleDOI
Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: Implications for gene therapy
Andre Larochelle,Josef Vormoor,Josef Vormoor,Helmut Hanenberg,Jean C.Y. Wang,Mickie Bhatia,Tsvee Lapidot,Tsvee Lapidot,Thomas Moritz,Barbara Murdoch,Xiang Li Xiao,Ikunoshin Kato,David R. Williams,John E. Dick +13 more
TL;DR: A novel human hematopoietic cell, the SCID–repopulating cell (SRC), a cell more primitive than most LTC–ICs and CFCs, that is capable of multilineage repopulation of the bone marrow of nonobese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice).
Journal ArticleDOI
c-kit Ligand and Flt3 Ligand: Stem/Progenitor Cell Factors With Overlapping Yet Distinct Activities
TL;DR: The daily turnover in a normal adult of approximately 1012 blood cells is tightly regulated, involving hematopoietic progenitor cells and mature blood cells from a pool of pluripotent, long-term reconstituting stem cells.
Journal ArticleDOI
Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene
Alfons Meindl,Heide Hellebrand,Constanze Wiek,Verena Erven,Barbara Wappenschmidt,Dieter Niederacher,Marcel Freund,Peter Lichtner,Linda Hartmann,Heiner Schaal,Juliane Ramser,Ellen Honisch,Christian Kubisch,Hans Erich Wichmann,Karin Kast,Helmut Deissler,Christoph Engel,Bertram Müller-Myhsok,Kornelia Neveling,Marion Kiechle,Christopher G. Mathew,Detlev Schindler,Rita K. Schmutzler,Helmut Hanenberg,Helmut Hanenberg +24 more
TL;DR: In index cases from 1,100 German families with gynecological malignancies, the first unambiguous evidence of highly penetrant mutations associated with human cancer in a RAD51 paralog is provided and support the 'common disease, rare allele' hypothesis.
References
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Journal ArticleDOI
Integrins: versatility, modulation, and signaling in cell adhesion.
Journal ArticleDOI
The Basic Science of Gene Therapy
TL;DR: A large number of key technical issues need to be resolved before gene therapy can be safely and effectively applied in the clinic, and future technological developments will be critical for the successful practice of gene therapy.
Journal ArticleDOI
T Lymphocyte-Directed Gene Therapy for ADA− SCID: Initial Trial Results After 4 Years
R. Michael Blaese,Kenneth W. Culver,A. Dusty Miller,Charles S. Carter,Thomas A. Fleisher,Mario Clerici,Gene M. Shearer,Lauren A. Chang,Yawen Chiang,Paul Tolstoshev,Jay J. Greenblatt,Steven A. Rosenberg,Harvey G. Klein,Melvin Berger,Craig A. Mullen,W. Jay Ramsey,Linda M. Muul,Richard A. Morgan,W. French Anderson +18 more
TL;DR: In this article, a clinical trial was started using retroviral-mediated transfer of the ADA gene into the T cells of two children with severe combined immunodeficiency (ADA-SCID).
Journal ArticleDOI
A safe packaging line for gene transfer: separating viral genes on two different plasmids.
TL;DR: Tests for recombination events that might result in intact retrovirus showed no evidence for the generation of replication-competent virus and results suggest that gag, pol, and env, when present on different plasmids, may provide an efficient and safe packaging line for use in retroviral gene transfer.