An important new collection of clinical and preclinical reports on genetic therapy, this book describes illustrative examples of diseases in which gene-based interventions are presently plausible, and presents case studies of current research using both synthetic oligonucleotides and biological vectors.
Combining the insights of over 50 contributors, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors

  • furnishes a historical overview of genetic therapy
  • highlights official Food and Drug Administration positions on the preparation of oligonucleotides and vectors
  • offers practical models of agent preparation, animal testing, pharmacokinetics, toxicology, and clinical trials
  • discusses both synthetic DNA and biological vector approaches to cancer, viral, and cardiological indications
  • illustrates for new practitioners how each stage of genetic therapy is developed
  • details genetic treatment of leukemia; lymphoma; cancer of the brain, breast, colon, kidney, and lung; melanoma; HIV; and coronary restenosis
  • includes examples of antisense, ribozyme, tumor suppressor, immunostimulation, and gene replacement therapy
  • and addresses questions of preparation, delivery, toxicity, mechanism, and specificity.
  • chapter 2|14 pages

    Preclinical Development of Antisense Oligonucleotide Therapeutics for Cancer: Regulatory Aspect

    ByChang-Ho Ahn, Joseph J. DeGeorge

    chapter 3|35 pages

    Commercial Scale Manufacturing of Oligonucleotides Under Good Manufacturing Practices

    ByJose E. Gonzalez, Richard G. Einig, Patricia Puma, Timothy P. Noonan, Paul E. Kennedy, Bruce G. Sturgeon, Bing H. Wang, Jin-yan Tang

    chapter 4|11 pages

    The Regulatory Process and Gene Therapy 1

    BySuzanne L. Epstein

    chapter 6|21 pages

    Gene Therapy Clinical Trials for Adenosine Deaminase Deficiency/Severe Combined Immunodeficiency

    ByEriinda M. Gordon, W. French Anderson

    chapter 7|21 pages

    Development of an Oligodeoxynucleotide Pharmaceutical for the Treatment of Human Leukemia

    ByAlan M. Gewirtz, Deborah Lee Sokol

    chapter 9|21 pages

    Human Bcl-2 Antisense Therapy for Lymphomas

    ByFinbarr E. Cotter, Andrew Webb, Paul Clarke, David Cunningham

    chapter 10|28 pages

    Retroviral Gene Transfer in Autologous Bone Marrow and Stem Cell Transplantation

    ByRafat Abonour, Kenneth Cornetta

    chapter 11|19 pages

    Adenoviral Gene Transfer of the Herpes Virus Thymidine Kinase Gene for Treating Gliomas

    ByJane Β. Alavi, Jason G. Smith, Stephen L. Eck

    chapter 12|17 pages

    Distribution and Toxicity of Retroviral Vectors after Intracavitary Delivery in Mouse and Man

    ByPatrice S. Obermiller, Carlos L. Arteaga, Jeffrey T. Holt, Anne M. Pilaro

    chapter 15|15 pages

    The Molecular Basis of Bladder Cancer and Prospects for Gene Therapy Using Hammerhead Ribozymes

    ByEric J. Small, Mohammed Kashani-Sabet, David Y. Bouffard, Kevin J. Scanlon

    chapter 16|20 pages

    In Situ Gene Insertion for Immunotherapy Using Vaccinia Virus Vectors

    ByEdmund C. Lattime, Laurence C. Eisenlohr, Michael J. Mastrangelo

    chapter 19|31 pages

    Synthetic DNA-Based Compounds for the Prevention of Coronary Restenosis: Current Status and Future Challenges

    ByAndrew Zalewski, Yi Shi, John D. Mannion, Femando Roqué

    chapter 20|18 pages

    Prevention of Restenosis by Gene Targeting

    ByMichael J. Mann, Victor J. Dzau, Heiko E. von der Leyen