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  • 1
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    Prospects for in utero human gene therapy (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-10-16
    Description: Gene therapy for the treatment of disease in children and adults is being actively pursued at many medical centers. However, a number of genetic disorders result in irreversible damage to the fetus before birth. In these cases, as well as for those with genetic diseases who may benefit from therapy before symptoms are manifested, in utero gene therapy (IUGT) could be beneficial. Although some successes with in utero gene transfer have been reported in animals, significant questions remain to be answered before IUGT clinical trials would be acceptable. This review analyzes the state of the art and delineates the studies that still need to be performed before it would be appropriate to consider human IUGT.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zanjani, E D -- Anderson, W F -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2084-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Veterans Administration Medical Center, University of Nevada, Reno, NV 89520, USA. zanjani@scs.unr.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10523208" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Fetal Diseases/*therapy ; *Fetus ; Gene Transfer Techniques ; Genetic Diseases, Inborn/*therapy ; *Genetic Therapy/adverse effects ; Genetic Vectors ; Germ Cells ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/cytology/physiology ; Humans ; Pregnancy
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    Gene therapy. The best of times, the worst of times (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-05-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, W F -- New York, N.Y. -- Science. 2000 Apr 28;288(5466):627-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Norris Cancer Center, Room 6316, University of Southern California, Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA. sdiaz@genome2.hsc.usc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10799000" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Deaminase/deficiency/genetics ; Antigens, CD34/analysis ; Cardiovascular Diseases/therapy ; Child, Preschool ; Clinical Trials as Topic ; Female ; Genetic Linkage ; *Genetic Therapy/adverse effects ; Genetic Vectors ; Hematopoietic Stem Cell Transplantation ; *Hematopoietic Stem Cells ; Hemophilia A/therapy ; Humans ; Infant ; Lymphocyte Count ; Neovascularization, Physiologic ; Receptors, Interleukin/biosynthesis/*genetics ; Severe Combined Immunodeficiency/enzymology/immunology/*therapy ; T-Lymphocytes/enzymology/immunology/transplantation ; Transfection ; X Chromosome
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Human gene therapy (1992)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1992-05-08
    Description: Human gene therapy is a procedure that is being used in an attempt to treat genetic and other diseases. Eleven clinical protocols are under way at the present time, each with scientific and clinical objectives. Human genetic engineering raises unique safety, social, and ethical concerns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, W F -- New York, N.Y. -- Science. 1992 May 8;256(5058):808-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1589762" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Deaminase/deficiency/*genetics ; Bioethics ; Clinical Trials as Topic ; Federal Government ; Female ; Genetic Diseases, Inborn ; Genetic Engineering ; *Genetic Therapy ; Government Regulation ; Humans ; Male ; Neoplasms/genetics/therapy ; Risk Assessment ; Safety ; Social Responsibility
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    High-level recombinant gene expression in rabbit endothelial cells transduced by retroviral vectors (1989)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1989-01-13
    Description: By virtue of its immediate contact with the circulating blood, the endothelium provides an attractive target for retroviral vector transduction for the purpose of gene therapy. To see whether efficient gene transfer and expression was feasible, rabbit aortic endothelial cells were infected with three Moloney murine leukemia virus-derived retroviral vectors. Two of these vectors carry genes encoding products that are not secreted: N2, containing only the selectable marker gene neoR, and SAX, containing both neoR gene and an SV40-promoted adenosine deaminase (ADA) gene. The third vector, G2N, contains a secretory rat growth hormone (rGH) gene and an SV40-promoted neoR gene. Infection with all three vectors resulted in expression of the respective genes. A high level of human ADA expression was observed in infected endothelial cell populations both before and after selection in G418. G2N-infected rabbit aortic endothelial cells that were grown on a synthetic vascular graft continued to secrete rGH into the culture medium. These studies suggest that endothelial cells may serve as vehicles for the introduction in vivo of functioning recombinant genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zwiebel, J A -- Freeman, S M -- Kantoff, P W -- Cornetta, K -- Ryan, U S -- Anderson, W F -- HL21568/HL/NHLBI NIH HHS/ -- HL33064/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1989 Jan 13;243(4888):220-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Hematology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2911735" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Deaminase/analysis/genetics ; Animals ; Aorta ; DNA, Recombinant/metabolism ; Endothelium, Vascular/*metabolism ; *Genes ; *Genes, Viral ; Genetic Markers/analysis ; *Genetic Vectors ; Growth Hormone/analysis/genetics ; Moloney murine leukemia virus/*genetics ; Promoter Regions, Genetic ; Rabbits ; Rats ; Recombinant Proteins/analysis ; *Transduction, Genetic ; *Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-10-20
    Description: In 1990, a clinical trial was started using retroviral-mediated transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA- SCID). The number of blood T cells normalized as did many cellular and humoral immune responses. Gene treatment ended after 2 years, but integrated vector and ADA gene expression in T cells persisted. Although many components remain to be perfected, it is concluded here that gene therapy can be a safe and effective addition to treatment for some patients with this severe immunodeficiency disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blaese, R M -- Culver, K W -- Miller, A D -- Carter, C S -- Fleisher, T -- Clerici, M -- Shearer, G -- Chang, L -- Chiang, Y -- Tolstoshev, P -- Greenblatt, J J -- Rosenberg, S A -- Klein, H -- Berger, M -- Mullen, C A -- Ramsey, W J -- Muul, L -- Morgan, R A -- Anderson, W F -- New York, N.Y. -- Science. 1995 Oct 20;270(5235):475-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Center for Human Genome Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7570001" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Deaminase/administration & ; dosage/blood/*deficiency/*genetics/therapeutic use ; Antibody Formation ; Base Sequence ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Gene Expression ; *Gene Transfer Techniques ; *Genetic Therapy ; Genetic Vectors ; Humans ; Immunity, Cellular ; Lymphocyte Count ; Lymphocyte Transfusion ; Lymphocytes/enzymology ; Molecular Sequence Data ; Severe Combined Immunodeficiency/enzymology/immunology/*therapy ; *T-Lymphocytes/enzymology/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Human gene therapy protocols: RAC review (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-06-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGarrity, G J -- Anderson, W F -- New York, N.Y. -- Science. 1995 Jun 2;268(5215):1261.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7761842" target="_blank"〉PubMed〈/a〉
    Keywords: *Advisory Committees ; *Clinical Protocols ; Clinical Trials as Topic ; *DNA, Recombinant ; Ethical Review ; Federal Government ; *Genetic Therapy ; *Government Regulation ; Humans ; *National Institutes of Health (U.S.)/organization & administration ; United States
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Site-directed neovessel formation in vivo (1988)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1988-09-09
    Description: Angiogenesis is an important component of organogenesis and wound repair and occurs during the pathology of oncogenesis, atherogenesis, and other disease processes. Thus, it is important to understand the physiological mechanisms that control neovascularization, especially with methods that permit the molecular dissection of the phenomenon in vivo. Heparin-binding growth factor-1 was shown to bind to collagen type I and type IV. When complexed with gelatin, heparin-binding growth factor-1 can induce neovascularization at polypeptide concentrations that are consistent with the biological activity of the mitogen in vitro. The adsorption strategy induces rapid blood vessel formation at and between organ- and tissue-specific sites and permits recovery of the site-specific implant for examination and manipulation by molecular methods.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, J A -- Anderson, K D -- DiPietro, J M -- Zwiebel, J A -- Zametta, M -- Anderson, W F -- Maciag, T -- HL32348/HL/NHLBI NIH HHS/ -- HL35627/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1988 Sep 9;241(4871):1349-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Hematology, National Heart, Lung and Blood Institute, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2457952" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Vessels/cytology ; Collagen/metabolism ; Extracellular Matrix ; Fibroblast Growth Factor 1 ; Gelatin/metabolism ; Growth Substances/*pharmacology ; Heparin/*pharmacology ; *Neovascularization, Pathologic ; Rats ; Tampons, Surgical
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Gene therapy researchers (1984)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1984-04-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, W F -- New York, N.Y. -- Science. 1984 Apr 27;224(4647):340.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17741202" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
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    Prospects for human gene therapy (1984)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1984-10-26
    Description: Procedures have now been developed for inserting functional genes into the bone marrow of mice. The most effective delivery system at present uses retroviral-based vectors to transfer a gene into murine bone marrow cells in culture. The genetically altered bone marrow is then implanted into recipient animals. These somatic cell gene therapy techniques are becoming increasingly efficient. Their future application in humans should result in at least partial correction of a number of genetic disorders. However, the safety of the procedures must still be established by further animal studies before human clinical trials would be ethical.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, W F -- New York, N.Y. -- Science. 1984 Oct 26;226(4673):401-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6093246" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Experimentation ; Bone Marrow ; Containment of Biohazards ; DNA Viruses/genetics ; *DNA, Recombinant ; Ethics Committees, Research ; Ethics, Medical ; Federal Government ; Gene Expression Regulation ; *Genes ; Genetic Diseases, Inborn/*therapy ; *Genetic Engineering ; Genetic Vectors ; Government Regulation ; Humans ; Microinjections ; Operon ; Plasmids ; Retroviridae/genetics ; Risk Assessment ; Skin ; Transcription, Genetic ; future clinical trials in humans are being debated among scientists and policy ; makers. Anderson, chief of the Laboratory of Molecular Hematology at the National ; Heart, Lung, and Blood Institute, examines how soon gene therapy might be ; available for the treatment of diseases in humans, and what criteria should be ; met before experimentation with human subjects begins. He identifies delivery, ; gene expression, and safety as the three requisites that must be satisfied, and ; reviews the animal work that has been done in these areas. Human trials should ; begin only after more animal studies have demonstrated to local and federal ; review committees that gene therapy is safe and offers the possibility of benefit ; to patients.
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    DNA-binding proteins (1983)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 1983-09-09
    Description: The structures of three proteins that regulate gene expression have been determined recently and suggest how these proteins may bind to their specific recognition sites on the DNA. One protein (Cro) is a repressor of gene expression, the second (CAP) usually stimulates gene expression, and the third (lambda repressor) can act as either a repressor or an activator. The three proteins contain a substructure consisting of two consecutive alpha helices that is virtually identical in each case. Structural and amino acid sequence comparisons suggest that this bihelical fold occurs in a number of proteins that regulate gene expression, and is an intrinsic part of the DNA-protein recognition event. The modes of repression and activation by Cro and lambda repressor are understood reasonably well, but the mode of action of CAP is still unclear.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takeda, Y -- Ohlendorf, D H -- Anderson, W F -- Matthews, B W -- GM20066/GM/NIGMS NIH HHS/ -- GM28138/GM/NIGMS NIH HHS/ -- GM30894/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1983 Sep 9;221(4615):1020-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6308768" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Chemical Phenomena ; Chemistry ; *DNA Helicases ; DNA-Binding Proteins ; Escherichia coli/genetics ; Gene Expression Regulation ; Models, Chemical ; Protein Conformation
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