Antiviral Gene Therapy
This chapter describes the major gene therapeutic approaches for viral infections. The vast majority of published approaches target severe chronic viral infections such as hepatitis B or C and HIV infection. Two basic gene therapy strategies are introduce
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Contents 1 2 3 4
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Basic Gene Therapeutic Approaches for Viral Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chronic Viral Infections as Targets for Antiviral Gene Therapy . . . . . . . . . . . . . . . . . . . . . . Gene Transfer Vectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Integrating Vectors Derived from Retroviruses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Genotoxicity of Integrating Vectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Nonintegrating Vectors Derived from Adenovirus, Adeno-Associated Virus, and HBV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Genes that Inhibit Viral Replication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Major Antiviral Gene Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Targets in the Viral Life Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3 Antiviral Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4 Antiviral RNAs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Clinical Trials Involving Intracellular Antiviral Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . 6.1 Stem Cell- vs. T Cell-Based Gene Therapy Strategies for HIV-Infection . . . . . . . . 6.2 Clinical Trials Involving T Cell Gene Transfer of Antiviral Genes . . . . . . . . . . . . . . 6.3 Clinical Trials Involving Stem Cell Gene Transfer of Antiviral Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Strategies to Potentially Overcome Insufficient Gene Marking . . . . . . . . . . . . . . . . . . . . . . 7.1 In Vivo Enrichment of Gene-Protected Cells by Coexpression of a Selectable Marker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2 Antiviral Gene Products with a Bystander Effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Gene Therapeutic Strategies that Act via Host Immune Effector Mechanisms . . . . . . . . . . 8.1 Enhancing Host Innate Immune Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2 Adoptive T Cell Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.3 Grafting T Cells with Recombinant Receptors to Enhance Virus-Specific Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4 Clinical Trials Employing TCR-Grafted T Cells . . . . . . . . . . . . . . . . . . . . . . . . . . .
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