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Lentiviral Vectors and Gene Therapy


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Table of Contents

1 Introduction to gene therapy.- 1.1 The concept of gene therapy.- 1.2 Origins of gene therapy.- 1.3 Gene therapy in the 1970s.- 1.4 Gene therapy in the 1980s.- 1.5 The breakthroughs in gene therapy from the 1990s and 2000s.- 1.6 Current human gene therapy and lentiviral vectors.- 1.7. Concluding remarks.- 2 Development of retroviral and lentiviral vectors.- 2.1 Retrovirus biology.- 2.2 Vectors based on -retroviruses.- 2.3 Vectors based on lentiviruses.- 2.4 Summary and conclusions.- 3 Cell and tissue gene targeting with lentiviral vectors.- 3.1 Introduction.- 3.2 Modification of lentivector tropism by pseudotyping (surface targeting).- 3.3 Transcriptional targeting.- 3.4 Post-transcriptional targeting.- 3.5 Conclusions.- 4 Immunomodulation by genetic modification using lentiviral vectors.- 4.1 Introduction to genetic immunotherapy.- 4.2 Lentivector gene therapy for immunization.- 4.3 Lentivector gene therapy for the treatment of autoimmune disease.- 4.4 Conclusions.- 5 Clinical grade lentiviral vectors.- 5.1 Introduction.- 5.2 Good manufacturing practise guidelines and clinical grade vector preparations.- 5.3 Scaling-up lentivector production for clinical application.- 5.4 Purity of clinical grade lentivectors.- 5.5 Biosafety.- 5.6 Final considerations and conclusions.- 6 Human gene therapy with retrovirus and lentivirus vectors.- 6.1 Introduction.- 6.2 Correction of Severe Combined Immunodeficiency-X1.- 6.3 Correction of X-linked chronic granulomatous disease.- 6.4 Correction of X-linked adrenoleukodystrophy.- 6.5 Correction of b-thalassaemia.- 6.6 Correction of Wiscott-Aldrich syndrome.- 6.7 Conclusions and final considerations.

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