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Wolff Gene Therapeutics



Methods and Applications of Direct Gene Transfer

Softcover Nachdruck of the original 1. Auflage 1994, 417 Seiten, Kartoniert, Paperback, Format (B × H): 155 mm x 235 mm, Gewicht: 663 g
ISBN: 978-1-4684-6824-3
Verlag: Springer, Basel


Wolff Gene Therapeutics

During the first half century of genetics, coinciding with the first half of this cen­ tury, geneticists dreamt of the repair of genetic disease by altering or replacing defective genes. H. J. Muller wrote of the great advantages of mutations, "nanoneedles" in his apt term, for delicately probing physiological and chemical processes. In the same spirit, genes could be used to provide treatments of needle point delicacy. Yet, during this period no realistic possibility appeared; it remained but a dream. The situation changed abruptly at the half century. Microbial genetics and its offshoot, cell culture genetics, provided the route. Pneumococcus transformation showed that exogenous DNA could become a permanent part of the genome; yet attempts to reproduce this in animals produced a few tantalizing hints of success, but mostly failures. Transduction, using a virus as mediator, offered a better op­ portunity. The fITSt reproducible in vivo gene therapy in a whole animal came in 1981. This was in Drosophila, with a transposable element as carrier. Flies were "cured" of a mutant eye color by incorporation of the normal allele, and the effect was transmissible, foreshadowing not only somatic, but germ line gene therapy. At the same time, retroviruses carrying human genes were found to be ex­ tremely efficient in transferring their contents to the chromosomes of cultured cells.

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I Background.- A History of Gene Transfer and Therapy.- Producing Mouse Genetic Models for Human Diseases.- Post-Transcriptional Considerations of Gene Expression: Translation, MRNA Stability, and Poly(A) Processing.- Promoters, Enhancers, and Inducible Elements for Gene Therapy.- II Methods and Mechanisms.- Possible Mechanisms of DNA Uptake in Skeletal Muscle.- Receptor-Mediated Gene Delivery Employing Adenovirus-Polylysine-DNA Complexes.- Gene Transfer in Mammalian Cells Using Liposomes as Carriers.- In Vivo Gene Therapy via Receptor-Mediated DNA Delivery.- Calcium Phosphate-Mediated DNA Transfection.- Cellular Internalization of Oligodeoxynucleotides.- Gene Transfer via Particle Bombardment: Applications of the Accell Gene Gun.- Electrically-Induced DNA Transfer Into Cells. Electrotransfection In Vivo.- III Applications.- Pharmacokinetic Considerations in the Use of Genes as Pharmaceuticals.- Virus-Mediated Genetic Treatment of Rodent Gliomas.- Gene Therapy for Adenosine Deaminase Deficiency and Malignant Solid Tumors.- Development of Herpes Simplex Virus Vectors for Gene Transfer to the Central Nervous System.- Direct Gene Transfer and Catheter Based Gene Delivery Systems: Applications to Cardiovascular Diseases and Malignancy.- Gene Therapy for Arthritis.- Gene Therapy: The Advent of Adenovirus.- In Vivo Gene Transfer Into the Heart.- Receptor-Mediated Targeted Gene Delivery Using Asialoglycoprotein-Polylysine Conjugates.- Retroviral-Mediated Gene Transfer and Duchenne Muscular Dystrophy.- Keyword Index.


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