Lentiviral Vector Systems for Gene Transfer

The human immunodeficiency viruses (HIVs), in particular HIV-1, are the causative agent responsible for the current worldwide epidemic of acquired immunodeficiency syndrome (AIDS). A major effort has thus been underway over the past two decades to understand and control this pathogen. During this time, an enormous knowledge base has accumulated regarding the role of viral factors in the HIV-1 life cycle, and the interaction of HIV-1 with the host cell is becoming increasingly understood. Certain features of HIV, for example its ability to infect non-dividing cells, are being exploited in the development of novel gene therapy vehicles. This volume provides an overview of the current information regarding the HIV replication cycle and will serve as an introduction to subsequent chapters that address specific aspects of lentiviral-based gene therapy.

Inhalt
Preface. 1: Introduction to Retroviruses and Retroviral Vectors; G.L. Buchschacher Jr. Introduction. General Background and Classification of Retroviruses. The Retrovirus Genome and Virion Structure. The Retrovirus Replication Cycle. Elements of Retroviral Vector Systems. Summary. Acknowledgements. 2: HIV-1 Replication; E.O. Freed. Introduction. The HIV-1 Replication Cycle. Role of the HIV Accessory Proteins in Virus Replication. Concluding Remarks. 3: Determinants for Lentiviral Infection of Non-Dividing Cells; M.A. Vodicka. Introduction. Nuclear Transport. Transit of Non-Retroviral Particles. Retroviral Preintegration Complexes. Assays for Infection of Non-Dividing Cells. Viral Protein Determinants for HIV-1 Infection of Non-Dividing Cells. Viral Genome Structural Determinants. Summary and Conclusions. 4: HIV-1 Vector Systems; N. Srinivasakumar. Introduction. HIV-1 Vector Systems Development. Clinical Applications of HIV-1 Vectors. Anticipated Developments in HIV-1-Based Packaging Systems and Possible Confounding Factors. Conclusions. Acknowledgements. 5: HIV-2 and SIV Vector Systems ; J.R. Gilbert, F. Wong-Staal. Introduction. Classification and Distribution. Pathology and Viral Replication. Genome Organization and Regulation. Vector Systems. Requiem and Prospectus. 6: Vector Systems; S.L. Sauter, M. Gasmi. Epidemiology and Pathogenesis of FIV Infection. Development of FIV-Based Vectors. Acknowledgements. 7: EIAV, CIAV and Other Lentevirus Vector Systems; J.C. Olsen. Introduction. Biological Similarities and Differences of Lenteviruses. Recent Vector Developments. 8: Safety Considerations in Vector Development. J.C. Kappes, Xiaoyun Wu. Introduction. Current Safety Design. Advancing Lenteviral Vectors Toward the Clinic. 9: Prospects for Gene Therapy Using HIV-Based Vectors ; Jiing-Kuan Yec, J.A. Zaia. Advantages of HIV Vectors Support Development. Attempts to Engineer Biosafety into HIV Vectors. Potential Clinical Applications of HIV Vectors. Regulatory Issues. Acknowledgements. 10: Ethical Considerations in the Use of Lenteviral Vectors for Genetic Transfer ; I. Roy. Introduction. Gene Therapy: Potentially Problematic Types of Application. General Ethical Considerations: Research and Clinical Settings. Summary. Index.

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