Drug Development for Gene Therapy

Yanmei Lu , Boris Gorovits 지음

Wiley 2024년 02월 08일 출간

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책소개

Drug Development for Gene Therapy Industry-centric perspective on translational and bioanalytical challenges and best practices for gene therapies Drug Development for Gene Therapy focuses on the translational and bioanalytical challenges and best practices for gene therapy modalities, presenting a significant body of data, including information related to safety and efficacy, necessary to advance through the development pipeline into clinical use. The text covers bioanalytical methods and platforms including patient screening assays, different PCR tests, enzyme activity assays, ELISpot, NGS, LC/MS, and immunoassays, with FDA and EMA guidelines on gene therapy safety and efficacy, along with companion diagnostics regulations from US and EU perspectives. The chapters offer an in-depth discussion of the basics and best practices for translational biomarkers, bioanalysis, and developing companion diagnostics / lab tests for gene therapies in the pharma and biopharma industries. To aid in reader comprehension, the text includes clinical examples of relevant therapies in related chapters. Some of the core topics covered include study design, immunogenicity, various bioanalytical methods and their applications, and global regulatory issues. Written by two highly qualified authors with significant experience in the field, Drug Development for Gene Therapy includes information on: Bioanalytical methods to detect pre-existing antibodies against adeno-associated viruses (AAV) capsids Detection of cellular immunity and humoral response to viral capsids and transgene proteins, and immunogenicity of gene therapy products Nonclinical and clinical study considerations and methods for biodistribution and shedding Quantification of transgene protein expression and biochemical function, and substrate and distal pharmacodynamic biomarker measurements for gene therapy Detection and quantification of rAA

목차

List of Contributors xix Preface xxiii Section I Introduction 1 1 Introduction to AAV-based in vivo Gene Therapy 3 Oscar Segurado 1.1 Introduction 3 1.1.1 History of Gene Therapy 3 1.1.2 AAV-based in vivo Gene Therapy: A Revolution in Medicine 4 1.1.3 The AAV Vector Structure 11 1.1.4 Cell Entry and Transduction Pathway 12 1.2 Advantages and Disadvantages for AAV in vivo 13 1.2.1 Effectiveness and Advantages of AAV Vectors for in vivo Gene Therapy 13 1.2.2 Challenges of AAV Vectors for in vivo Gene Therapy 14 1.3 Technology Platforms of AAV-based in vivo Gene Therapy 14 1.3.1 cDNA Replacement 15 1.3.2 Genome Editing 15 1.3.2.1 Zfn 16 1.3.2.2 TALENs 16 1.3.2.3 CRISPR/Cas 9 16 1.3.3 Base Editing and Prime Editing 17 1.3.4 RNAi Gene Silencing 17 1.3.5 Gene Addition 18 1.4 AAV Serotypes and Tissue Affinity 18 1.4.1 The Liver as a Biofactory 19 1.4.2 The CNS as a Biofactory 19 1.4.3 The Muscle as a Biofactory 19 1.5 Precision Medicine: Screening and Monitoring Biomarkers, Companion Diagnostics 19 1.5.1 Gene Therapy Clinical Trials: Spotlight on Hemophilia A 20 1.6 Predictions for Scientific and Medical Progress 22 1.6.1 Predictions for Challenges in the Field 22 1.6.2 Addressing Durability 23 1.6.3 Addressing Immunogenicity 24 1.6.4 Addressing Malignancy 24 1.7 Predictions for Market Adoption 24 1.7.1 Patients and Patient Advocacy Groups 25 1.7.2 Physicians, Clinical Guidelines, Regulatory Agencies 25 1.7.3 Payers 26 1.8 Final Thoughts 26 1.8.1 Can We Afford in vivo Gene Therapies? 26 1.8.2 Can in vivo Gene Editing Replace Gene Therapy? 27 References 28 2 Recent Development in in vivo Clinical Gene Therapy Platforms 35 John Murphy and Jane Owens

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저자(글) Yanmei Lu

저자(글) Boris Gorovits

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