Gene Therapy - Technologies, Markets & Companies

Table of Contents

Gene Therapy
Part I: Technologies & Markets

Executive Summary 

1. Introduction

• Definitions
• Historical evolution of gene therapy 
• Relation of gene therapy to other biotechnologies. 
• Molecular biological basics for gene therapy
• Genome 
• DNA
• RNA
• Transcriptome  
• RNA splicing
• Genes
• Silent gene mutations 
• Gene regulation
• Gene expression 
• ENCODE
• Chromosomes
• Telomeres
• Mitochondria
• Proteins 

2. Gene Therapy Technologies 

• Classification of gene therapy techniques 
• Ex vivo and in vivo gene therapy
• Ex vivo gene therapy  
• In vivo gene therapy  
• Physical methods of gene transfer
• Electroporation  
• Applications of electroporation
• Clinical applications of electroporation
• Advantages of electroporation 
• Limitations of electroporation
• Hydrodynamic
• Microinjection 
• Particle bombardment 
• Ultrasound-mediated transfection 
• Molecular vibration
• Application of pulsed magnetic field and superparamagnetic nanoparticles 
• Gene transfection using laser irradiation
• Photochemical transfection  
• Chemical methods of gene transfer
• Vectors for gene therapy
• Basic considerations
• Use of genes as pharmaceuticals
• The ideal vector for gene therapy
• Viral vectors  
• Adenovirus vectors 
• Adeno-associated virus vectors
• Alphavirus vectors... 
• Baculovirus vectors
• Foamy virus vectors  
• Herpes simplex virus vectors  
• Lentiviral vectors  
• Multicistronic retroviral vectors
• Retroviral vectors  
• Oncogenic potential of retroviral vectors  
• Quantification of viral vectors
• Future of viral vectors
• Companies using viral vectors 
• Nonviral vectors for gene therapy 
• Anionic lipid-DNA complexes  
• Cationic lipid-DNA complexes
• Effects of shape of DNA molecules on delivery with nonviral vectors 
• Electrostatic modifications of surface to improve gene delivery
• Liposomes for gene therapy
• Liposome-nucleic acid complexes 
• Liposome-HVJ complex  
• Transposons DNA vectors. 
• Polycation-DNA complexes (polyplexes)
• Plasmid DNA vs minicircle DNA
• Polymer vectors for gene therapy.. 
• Synthetic biology and DNA vectors  
• Synthetic peptide complexes  
• Future of nonviral vs viral vectors
• Nanobiotechnology for gene therapy 
• Antisense nanoparticles
• Dendrimers  
• Cochleates
• Calcium phosphate nanoparticles as nonviral vectors
• DNA nanoparticles as nonviral vectors
• Gelatin nanoparticles for gene delivery 
• Lipid nanoparticles for nucleic acid delivery  
• Nanoparticles as nonviral vectors for gene therapy 
• Nanoparticles with virus-like function as gene therapy vectors 
• Nanobiolistics for nucleic acid delivery
• Nonionic polymeric micelles for oral gene delivery
• Silica nanoparticles as a nonviral vector for gene delivery  
• Virus-like particles as nonviral vector  
• Receptor-mediated endocytosis
• Artificial viral vectors  
• Directed evolution of AAV to create efficient gene delivery vectors
• Bacterial ghosts as DNA delivery systems
• Bacteria plus nanoparticles for gene delivery into cells 
• Chromosome-based vectors for gene therapy 
• Mammalian artificial chromosomes (MACs)
• Human artificial chromosomes (HACs)
• ΦC31 integrase system  
• Companies using nonviral vectors 
• Concluding remarks about vectors
• Gene repair and replacement
• Gene repair by single-stranded oligonucleotides... 
• History and current status of chimeraplasty  
• Genome editing
• Gene editing by zinc finger nucleases
• Gene editing by using short synthetic oligonucleotides 
• Genome engineering by using TALENs  
• Genome editing by homologous recombination  
• GeneRide technology for genome editing
• Gene editing by homing endonucleases 
• ARCUS genome editing technology  
• Genome editing by using CRISPR system  
• A method for generating genome-wide gRNA libraries for CRISPR
• CRISPR-genome organization system  
• CRISPR vs other gene editing tools
• CRISPR-FRT
• CRISPR for studying human embryogenesis
• CRISPER system for creating animal models of human diseases  
• CRISPR/Cas9 technology for drug discovery
• CRISPR/Cas9-mediated epigenetic editing system
• Expanding the range of Cas9s 
• Inducible CRISPR/Cas9 for multiple gene targeting
• Lipid nanoparticles for delivery of CRISPR-Cas9 for genome-editing 
• Nanocapsules for delivery of CRISPR-Cas9 for genome editing 
• Nano-CRISPR
• Photoactivatable CRISPR-Cas9 
• Protein delivery and genome editing 
• Potential clinical applications of CRISPR systems 
• Autosomal dominant retinitis pigmentosa
• Clinical trial of CRISPR in human cancer. 
• CRISPR for glioblastoma 
• Correction of a gene mutation in the human embryo
• Glaucoma 
• PERV blockage by CRISPR to facilitate xenotransplantation 
• RNA editing with CRISPR.. 
• Use of CRISPR for β-hemoglobinopathies
• Use of CRISPR to restore hereditary hearing loss  
• Complications and limitations of CRISPR/Cas9 technology  
• Companies developing CRISPR technology
• Clinical studies of gene editing
• Targeted genome editing by artificial nucleases
• Ex vivo gene editing
• DNA medicines based on gene editing 
• Comparison of gene editing with techniques for suppression of gene mutations
• Future of gene editing  
• Base editing of the genome
• Base editing by protein engineering.. 
• Adenine base editors for genomic DNA
• Messenger RNA gene therapy 
• Spliceosome mediated RNA trans-splicing
• Cell-mediated gene therapy
• Fibroblasts  
• Skeletal muscle cells 
• Vascular smooth muscle cells 
• Keratinocytes  
• Hepatocytes 
• Lymphocytes
• Regulating protein delivery by genetically encoded lymphocytes
• Implantation of microencapulated genetically modified cells  
• Stem cell gene therapy
• Combination of gene therapy with therapeutic cloning
• Expansion of transduced HSCs in vivo
• Gene delivery to stem cells by artificial chromosome expression
• Improving delivery of genes to stem cells  
• In utero gene therapy using stem cells  
• Lentiviral vectors for gene transfer to marrow stem cells
• Linker based sperm-mediated gene transfer technology
• Mesenchymal stem cells for gene therapy  
• Microporation for transfection of MSCs
• Preventing immune rejection of transplanted stem cells
• Therapeutic applications for hematopoietic stem cell gene transfer 
• Transdermal gene therapy for drug addiction
• The future of hematopoietic stem cell gene therapy 
• Chimeric antigen receptor T cells in relation to gene therapy 
• Basics of CAR-T cell  
• Basis of anticancer effect of CAR-T cells  
• Smart T-cells  
• CAR-T cell manufacture 
• Companies developing CAR-T cell therapy
• CAR NK cells derived from human iPSCs
• Genome editing of CAR-T cells
• Safety and efficacy of CAR-T cell therapy 
• Cytokine release syndrome  
• Precautions for CAR-T cell therapy 
• Role of genetically modified bacteria in gene therapy
• Routes of administration for gene therapy 
• Direct injection of naked DNA 
• Intramuscular injection
• Intravenous DNA injection 
• Intraarterial delivery 
• Companies with gene delivery devices/technologies
• Targeted gene therapy
• Targeted integration
• Bacteriophage integrase system for site-specific gene delivery  
• Controlled-release delivery of DNA
• Controlled gene therapy 
• Controlled delivery of genetic material 
• Controlled induction of gene expression  
• Drug-inducible systems for control of gene expression  
• Timed activation of gene therapy by a circuit based on signaling network
• Small molecules for post-transcriptional regulation of gene expression
• Light Activated Gene Therapy 
• Spatial control of gene expression via local hyperthermia  
• Companies with regulated /targeted gene therapy
• Gene marking 
• Germline gene therapy  
• Potential applications of human germline genome modification  
• Pros and cons of human germline genome modification 
• Role of gene transfer in antibody therapy  
• Genetically engineered vaccines 
• DNA vaccines  
• DNA inoculation technology  
• Methods for enhancing the potency of DNA vaccines
• Advantages of DNA vaccines 
• Vaccine vectors
• Challenges and limitations of genetically engineered vaccines 
• RNA vaccines. 
• Nonviral delivery of self-amplifying RNA vaccine
• Vaccines based on reverse genetics 
• Technologies for gene suppression 
• Antisense oligonucleotides 
• Transcription factor decoys
• Aptamers 
• Ribozymes  
• Peptide nucleic acid  
• Intracellular delivery of PNAs 
• Locked nucleic acid  
• Zorro-LNA  
• Gene silencing
• Post-transcriptional gene silencing
• Definitions and terminology of RNAi
• RNAi mechanisms 
• Inhibition of gene expression by antigene RNA 
• RNAi gene therapy
• microRNA gene therapy 
• Viral vectors for RNAi and miRNA gene therapy
• Application of molecular diagnostic methods in gene therapy
• Use of PCR to study biodistribution of gene therapy vector 
• PCR for verification of the transcription of DNA 
• In situ PCR for direct quantification of gene transfer into cells
• Detection of retroviruses by reverse transcriptase (RT)-PCR  
• Confirmation of viral vector integration
• Monitoring of gene expression
• Monitoring of gene expression by green fluorescent protein  
• Monitoring in vivo gene expression by molecular imaging
• Advantages of gene therapy compared with protein therapy
• Formulation, transport, and storage of materials for gene therapy

3. Clinical Applications of Gene Therapy

• Introduction  
• Aging-related disorders
• Telomerase gene therapy in aging
• Combination gene therapy for treatment of multiple age-related diseases
• Bone and joint disorders 
• Bone fractures
• Gene therapy for intervertebral disc degeneration 
• Spinal fusion
• Osteogenesis imperfecta
• Rheumatoid arthritis
• Local or systemic treatment
• In vivo or ex vivo gene therapy of RA 
• Clinical trials of gene therapy for rheumatoid arthritis  
• Gene therapy for osteoarthritis  
• Gene therapy strategies for osteoarthritis  
• Clinical trials of gene therapy for osteoarthritis
• Sports injuries
• Repair of articular cartilage defects
• Regeneration and replacement of bone by gene therapy
• Bacterial infections 
• Antisense approach to bacterial infections
• Dentistry 
• Tissue engineering in dental implant defects
• Endocrine and metabolic disorders 
• Introduction 
• Gene therapy of obesity 
• AAV vector-mediated delivery of GDNF for obesity  
• Oligopeptide for targeted nonviral gene delivery to adipocytes  
• Viral vector-mediated leptin gene therapy  
• Diabetes mellitus
• Methods of gene therapy of diabetes mellitus  
• Viral vector-mediated gene transfer in diabetes  
• Endogenous reprogramming of α cells into  cells
• Gene delivery with ultrasonic microbubble destruction technology
• Genetically engineered cells for diabetes mellitus 
• Genetically altered liver cells 
• Genetically modified stem cells
• Genetically engineered dendritic cells 
• Glucokinase and insulin co-expression
• Leptin gene therapy 
• Concluding remarks about cell and gene therapy of diabetes 
• Gene therapy of growth-hormone deficiency
• Gastrointestinal disorders 
• Introduction 
• Methods of gene transfer to the gastrointestinal tract
• Direct delivery of genes
• Naked plasmid DNA into the submucosa 
• Viral vectors
• Receptor-mediated endocytosis 
• Indications for gastrointestinal gene therapy
• Gene therapy for inflammatory disorders of the bowel
• Gene transfer to the salivary glands
• Potential clinical applications of salivary gene therapy
• Hematology
• Hemophilias 
• Gene therapy of hemophilia
• Hemophilia A  
• Hemophilia B  
• Concluding remarks about gene therapy of hemophilias
• Hemoglobinopathies
• Gene therapy for β-thalassemia 
• Gene therapy for sickle cell disease
• HSC-targeted gene therapy for SCD  
• Gene therapy and RNAi for SCD based on stem cells
• Gene editing in sickle cell disease
• Gene editing using ZFN as treatment for both SCD and β-thalassemia
• Gene editing using CRISPR-Cas9 for both SCD and β-thalassemia
• Gene therapy of Fanconi's anemia
• Acquired hematopoietic disorders
• Chronic acquired anemias 
• Neutropenia
• Thrombocytopenia  
• Concluding remarks about gene therapy of hemoglobinopathies 
• Companies involved in gene thery of hematological disorders 
• In utero/fetal gene therapy
• Fetal gene transfer techniques
• Animal models of fetal gene therapy  
• Potential applications of fetal gene therapy
• Fetal gene therapy for cystic fibrosis
• Fetal intestinal gene therapy 
• Gene therapy for fetal growth restriction 
• Hearing disorders  
• Potential of gene therapy  
• Vectors for gene therapy of hearing disorders  
• Auditory hair cell replacement and hearing improvement by gene therapy  
• Kidney diseases
• End-stage renal disease 
• Methods of gene delivery to the kidney
• Bone marrow stem cells for renal disease  
• Gene transfer into kidney by viral vectors  
• Gene transfer into the glomerulus by HVJ-liposome
• Gene transfer to tubules with cationic polymer polyethylenimine
• Liposome-mediated gene transfer into the tubules  
• Mesangial cell therapy
• Non-viral gene transfer to the kidneys
• Gene therapy in animal experimental models of renal disease
• Genetic manipulations of the embryonic kidney
• Antisense intervention in glomerulonephritis
• Gene therapy for renal fibrosis  
• Use of genetically engineered cells for uremia due to renal failure  
• Concluding remarks
• Liver disorders
• Techniques of gene delivery to liver
• Direct injection of DNA into liver
• Local gene delivery by isolated organ perfusion  
• Liposome-mediated direct gene transfer 
• Retroviral vector for gene transfer to liver  
• Adenoviral vectors for gene transfer to liver
• Receptor-mediated approach 
• Cell therapy for liver disorders
• Transplantation of genetically modified hepatocytes 
• Genetically modified hematopoietic stem cells 
• Gene therapy by ex vivo transduced liver progenitor cells 
• Gene therapy of genetic diseases affecting the liver
• Crigler-Najjar syndrome  
• Hereditary tyrosinemia type I (HT1)  
• Hereditary tyrosinemia type 3  
• Wilson’s disease  
• Gene therapy of acquired diseases affecting the liver
• Cirrhosis of liver
• Ophthalmic disorders
• Introduction to gene therapy of ophthalmic disorders
• Methods of gene therapy for ophthalmic disorders
• Delivery of gene therapy by intravitreal injection 
• DNA nanoparticles for nonviral gene transfer to the eye
• Optogenetic gene therapy for blindness due to retinal degeneration  
• Age-related macular degeneration
• Inherited disorders of optic nerve affecting vision 
• Leber hereditary optic neuropathy
• Gene therapy for LHON 
• Inherited retinal degenerations  
• Choroideremia 
• Leber congenital amaurosis  
• Monogenic macular degeneration due to mutations in the BEST1 gene  
• Retinitis pigmentosa 
• Stargardt disease 
• Other inherited disorders affecting vision 
• Color blindness
• Usher syndrome
• X-linked retinoschisis
• Diabetic retinopathy
• Future of gene therapy of inherited retinal degenerations
• Combining cell and gene therapies for retinal disorders.. 
• Prevention of complications associated with eye surgery
• Prevention of proliferative retinopathy by gene therapy
• Posterior capsule opacification after cataract surgery
• Autoimmune uveitis
• Retinal ischemic injury  
• Corneal disorders
• Glaucoma
• Corneal scarring  
• Companies developing gene therapy for eye disorders  
• Organ transplantation 
• Introduction 
• DNA vaccines for transplantation
• Gene therapy for prolonging allograft survival
• Genetically modified Tregs expressing CAR for preventing GVHD  
• Gene therapy in lung transplantation  
• Role of gene therapy in liver transplantation
• Gene therapy in kidney transplantation. 
• Veto cells and transplant tolerance
• Pulmonary disorders  
• Techniques of gene delivery to the lungs 
• Adenoviral vectors  
• Nonviral vectors  
• Aerosolization as an aid to gene transfer to lungs.  
• Cystic fibrosis  
• Genetics and clinical features
• Gene therapy for CF 
• CFTR gene transfer in CF
• Concluding remarks about gene therapy of CF 
• Miscellaneous pulmonary disorders 
• Gene therapy for pulmonary arterial hypertension
• Gene therapy for bleomycin-induced pulmonary fibrosis  
• Gene therapy of emphysema due to α1-antitrypsin deficiency  
• Gene therapy for asthma
• Gene therapy for adult respiratory distress syndrome  
• Gene therapy for lung injury 
• Gene therapy for bronchopulmonary dysplasia 
• Concluding remarks about gene therapy of lungs
• Companies involved in pulmonary gene therapy  
• Skin and soft tissue disorders 
• Gene transfer to the skin  
• Electroporation for transdermal delivery of plasmid DNA  
• Electroporation for transdermal delivery of DNA vaccines
• Liposomes for transdermal gene delivery
• Ultrasound and topical gene therapy
• Gene therapy in skin disorders  
• Gene therapy of hair loss
• Gene therapy for epidermolysis bullosa  
• Gene therapy for xeroderma pigmentosa
• Gene therapy for lamellar ichthyosis  
• Gene transfer techniques for wound healing 
• Urogenital disorders  
• Gene therapy for urinary tract dysfunction  
• Gene therapy for erectile dysfunction
• NOS gene transfer for erectile dysfunction
• Clinical trial of hMaxi-K Gene transfer in erectile dysfunction 
• Gene therapy for erectile dysfunction due to nerve injury... 
• Concluding remarks on gene therapy for erectile dysfunction 
• Gene therapy of miscellaneous disorders  
• Primary Sjögren's syndrome  
• Veterinary gene therapy 
• Gene therapy for mucopolysaccharidosis VII in dogs 
• Gene therapy to increase disease resistance.. 
• Gene therapy for infections
• Gene therapy for chronic anemia
• Gene therapy for endocrine disorders
• Gene therapy for arthritis 
• Cancer gene therapy 
• Brain tumors in cats and dogs  
• Breast cancer in dogs  
• Canine hemangiosarcoma 
• Canine melanoma
• Canine soft tissue sarcoma
• Melanoma in horses

4. Gene Therapy of Genetic Disorders

• Introduction  
• Primary immunodeficiency disorders
• Severe combined immune deficiency  
• Gene therapy for SCID 
• Lentiviral gene therapy combined with low-dose busulfan for SCID-X1  
• Chronic granulomatous disease
• Wiskott-Aldrich syndrome
• Purine nucleoside phosphorylase deficiency
• Major histocompatibility class II deficiency  
• Future prospects of gene therapy of inherited immunodeficiencies
• Metabolic disorders.. 
• Alpha1-antitrypsin deficiency
• AAV mediated gene therapy for α1-antitrypsin deficiency
• iPSCs for targeted gene correction of α1-antitrypsin deficiency
• Gene editing for AAT deficiency 
• Adrenoleukodystrophy  
• Canavan disease  
• Lesch-Nyhan syndrome 
• Lipoprotein lipase deficiency  
• Alipogene tiparvovec
• Ornithine transcarbamylase deficiency 
• Gene therapy for OTCD 
• AAV-mediated gene editing for OTCD using CRISPR-Cas9 
• Phenylketonuria
• Porphyrias  
• Tetrahydrobiopterin deficiency
• Lysosomal storage disorders. 
• Batten disease
• Fabry's disease 
• Farber’s disease
• Gaucher disease  
• Animals models of Gaucher's disease... 
• Gene therapy of Gaucher's disease 
• Glycogen storage disorders
• Glycogen storage disease type I
• Gene therapy of GSD1a
• Hunter syndrome
• Krabbe's disease  
• Metachromatic leukodystrophy  
• Mucopolysaccharidosis type 1 (Hurler syndrome)
• Niemann-Pick type A disease
• Pompe disease 
• Sanfilippo A syndrome  
• Sly syndrome  
• Tay-Sachs disease/Sandhoff disease  
• Future of gene therapy of lysosomal storage disorders
• Trinucleotide repeat disorders
• Muscular dystrophies
• Duchenne muscular dystrophy (DMD)
• Animal models for gene therapy of DMD 
• Antisense approaches to DMD. 
• CRISPR/Cas9 gene editing for DMD
• Exon-skipping for DMD 
• Galgt2 gene therapy 
• Liposome-mediated gene transfer
• Microdystrophin gene therapy
• Myoblast-based gene transfer in DMD 
• Plasmid-mediated gene therapy 
• Purinoreceptor P2RX7 ablation  
• Post-transcriptional modulation of gene expression in DMD  
• Repair/Editing of dystrophin gene
• Routes of administration of gene therapy in DMD 
• Types of dystrophin constructs
• Viral vectors for DMD  
• Conclusions and future of gene therapy of DMD  
• Limb-girdle muscular dystrophy
• Myotonic dystrophy  
• Spinal muscular atrophy
• Gene therapy strategies for SMA
• Zolgensma® gene therapy for SMA
• Antisense approaches for SMA  
• Nusinersen
• Nusinersen vs Zolgensma® gene therapy for SMA  
• X-linked myotubular myopathy (XLMTM)... 
• Hereditary neuropathies 
• Charcot-Marie-Tooth disease
• Hereditary axonal neuropathies of the peripheral nerves
• Gene editing for hereditary transthyretin amyloidosis
• Current therapies for ATTR amyloidosis  
• CRISPR-Cas9 gene editing for ATTR amyloidosis  
• Gene therapy of mitochondrial disorders
• Techniques for mitochondrial replacement therapy
• Status of mitochondrial replacement and transfer therapies  
• Barth syndrome
• Companies involved in gene therapy of genetic disorders

5. Gene Therapy of Cancer 

• Strategies for cancer gene therapy 
• Direct gene delivery to the tumor  
• Injection into tumor
• Direct injection of adenoviral vectors
• Direct injection of a plasmid DNA-liposome complex 
• A polymer approach to local gene therapy for cancer
• Electroporation for cancer gene therapy  
• Control of gene expression in tumor by local heat 
• Radiation-guided gene therapy of cancer 
• Radioprotective gene therapy of cancer  
• Nanoparticles to facilitate combination of hyperthermia and gene therapy
• Immunogene therapy of cancer
• Cell-based cancer gene therapy
• Adoptive cell therapy 
• CAR-T cell therapy for cancer 
• CAR-T cells for tumor targeting
• CAR-T cells targeting both CD19 and CD22 
• Remote control of CAR-T cells for cancer immunotherapy 
• CAR-T cell therapy for leukemia 
• CAR-T cell therapy for multiple myeloma
• CAR-T cell therapy for lymphoma  
• CAR-T cell therapy for solid tumors
• Cytokine gene therapy  
• Genetic modification of human hematopoietic stem cells
• Cancer vaccines
• Genetically modified cancer cell vaccines 
• GVAX cancer vaccines
• Genetically modified dendritic cells 
• Nucleic acid-based cancer vaccines 
• DNA cancer vaccines
• RNA vaccines  
• Viral vector-based cancer vaccines
• Intradermal delivery of cancer vaccines by Ad vectors
• Vaccines based on genetically engineered nonviral vectors 
• Future of cancer vaccines  
• Companies involved in nucleic acid-based cancer vaccines 
• Monoclonal antibody gene transfer for cancer
• Transfer and expression of intracellular adhesion-1 molecules
• Other gene therapy techniques for immunotherapy of cancer
• Chemokines 
• CRISPR for immunogene therapy
• Engineered viruses as anticancer immunotherapy vectors
• Fas (Apo-1)
• Major Histocompatibility Complex (MHC) Class I  
• IGF (Insulin-Like Growth Factor) 
• Cancer immunotherapies targeting multiple mechanisms 
• Inhibition of immunosuppressive function in cancer
• Delivery of toxic genes to tumor cells for eradication 
• Gene-directed enzyme prodrug therapy  
• Combination of gene therapy with radiotherapy 
• Correction of genetic defects in cancer cells  
• Targeted gene therapy for cancer  
• Antiangiogenic therapy for cancer  
• Bacteria as novel anticancer gene vectors
• Cancer-specific gene expression 
• Cancer-specific transcription 
• Delivery of retroviral particles hitchhiking on T cells
• Electrogene and electrochemotherapy 
• Epidermal growth factor-mediated DNA delivery  
• Gene expression in hypoxic tumor cells  
• Genetically modified T cells for targeting tumors  
• Genetically engineered stem cells for targeting tumors
• Hematopoietic stem cells for targeted cancer gene therapy
• Immunolipoplex for delivery of p53 gene 
• Nanomagnets for targeted cell-based cancer gene therapy 
• Nanoparticles for targeted site-specific delivery of anticancer genes
• Targeted cancer therapy using a dendrimer-based synthetic vector 
• Tumor-targeted gene therapy by receptor-mediated endocytosis
• Virus-mediated oncolysis
• Cytokine-induced killer cells for delivery of an oncolytic virus 
• Monitoring of viral-mediated oncolysis by PET
• Oncolytic adenoviruses
• Oncolytic HSV  
• Oncolytic measles viruses
• Oncolytic vaccinia virus... 
• Oncolytic vesicular stomatitis virus
• Targeted cancer treatments based on oncolytic viruses... 
• Concluding remarks on oncolytic gene therapy 
• Companies developing oncolytic viruses  
• Apoptotic approach to improve cancer gene therapy
• Tumor suppressor gene therapy 
• P53 gene therapy... 
• BRIT1 gene therapy
• Nitric oxide-based cancer gene therapy
• Anticancer effect of nitric oxide synthase 
• Gene therapy for radiosensitization of cancer  
• Gene therapy of cancer of selected organs 
• Gene therapy for bladder cancer 
• Gene therapy for glioblastoma
• Adenoviral vectors for treatment of brain tumors 
• Antiangiogenic gene therapy 
• Autophagy induced by conditionally replicating adenoviruses 
• Baculovirus vector for diphtheria toxin gene therapy
• Cerepro® (sitimagene ceradenovec)
• Gene therapy targeting hepatocyte growth factor 
• Genetically engineered MSCs for gene delivery to intracranial gliomas
• Intravenous gene delivery with nanoparticles into brain tumors 
• Ligand-directed delivery of dsRNA molecules targeted to EGFR
• Olig2 targeting to hinder growth of treatment-resistant glioblastomas
• Oncolytic immunovirotherapy for pediatric high-grade gliomas
• RNAi gene therapy of brain cancer 
• Targeting normal brain cells with an AAV vector encoding interferon-β  
• Viral oncolysis of glioblastoma multiforme  
• Gene therapy for breast cancer  
• Gene vaccine for breast cancer
• Recombinant adenoviral ErbB-2/neu vaccine  
• Gene Therapy for ovarian cancer
• Gene therapy for malignant melanoma
• Immunogene therapy  
• Nonviral immunogene therapy for malignant melanoma
• Oncogene targeted therapy  
• Targeted gene therapy for malignant melanoma
• Gene therapy of lung cancer 
• Intravenous nanoparticle formulation for delivery of FUS1 gene 
• Aerosol gene delivery for lung cancer 
• Gene therapy for cancer of prostate
• Experimental studies
• Nanoparticle-based gene therapy for prostate cancer  
• Tumor suppressor gene therapy in prostate cancer
• Vaccines for prostate cancer
• Viral oncolysis for prostate cancer
• Clinical trials of gene therapy for prostate cancer 
• Gene therapy of head and neck cancer
• Adenoviral vector based P53 gene therapy
• Gene therapy as adjunct to 5-FU for nasopharangeal carcinoma
• Gene therapy of pancreatic tumors 
• Pancreatic neuroendocrine tumors 
• Pancreatic ductal adenocarcinoma
• Editing of altered genes
• Targeted gene therapy 
• Targeting in pancreatic adenocarcinoma with cell surface antigens 
• Targeted Expression of BikDD gene
• Viral oncolysis in pancreatic cancer
• Concluding remarks on gene therapy of pancreatic cancer
• Gene therapy of renal cancer... 
• Viral onclolytic therapy for renal cancer
• Gene therapy of hematological malignancies
• Genetically engineered T lymphocytes
• Cancer gene therapy companies 

6. Gene Therapy of Neurological Disorders

• Indications 
• Gene transfer techniques for the nervous system  
• Methods of gene transfer to the nervous system  
• Ideal vector for gene therapy of neurological disorders
• Promoters of gene transfer 
• Lentivirus-mediated gene transfer to the CNS
• AAV vector mediated gene therapy for neurogenetic disorders
• Gene transfer to the CNS using recombinant SV40-derived vectors 
• Routes of delivery of genes to the nervous system
• Direct injection into CNS  
• Introduction of the genes into cerebral circulation
• Introduction of genes into cerebrospinal fluid
• Intravenous administration of vectors 
• Delivery of gene therapy to the peripheral nervous system
• Cell-mediated gene therapy of neurological disorders
• Neuronal cells
• Neural stem cells and progenitor cells 
• Astrocytes  
• Cerebral endothelial cells
• Implantation of genetically modified encapsulated cells into the brain 
• Gene transfer for neuromodulation
• Monitoring of CNS gene therapy 
• Gene therapy of neurodegenerative disorders
• Gene therapy for Parkinson disease 
• Rationale 
• Techniques of gene therapy for PD 
• Augmenting CNS glucocerebrosidase activity  
• Delivery of neurotrophic factors by gene therapy 
• Delivery of parkin gene 
• Gene editing in PD  
• Introduction of functional genes into the brain of patients with PD 
• Nanoparticle-based gene therapy for PD 
• Mitochondrial gene therapy for PD
• RNAi approach to PD
• Viral vector-based ubiquitination to prevent spread of α-synuclein 
• Prospects of gene therapy for PD  
• Concluding remarks about gene therapy of PD 
• Companies developing gene therapy for PD 
• Gene therapy for Alzheimer disease
• Rationale
• NGF gene therapy for AD
• FGF2 gene transfer in AD
• Gene therapy for restoring brain cholesterol metabolism
• Neprilysin gene therapy
• Viral gene transfer of APPsα for rescuing synaptic failure in AD
• Gene vaccination 
• Combination of gene therapy with other treatments for AD  
• Gene therapy of Huntington disease
• Encapsulated genetically engineered cellular implants 
• Viral vector mediated administration of neurotrophic factors 
• RNAi gene therapy  
• Gene therapy of amyotrophic lateral sclerosis  
• Rationale
• Technique of gene therapy of ALS
• Other approaches to gene therapy of ALS  
• Gene therapy of cerebrovascular diseases
• Preclinical research in gene therapy for cerebrovascular disease 
• Animal models of stroke relevant to gene therapy 
• Transgenic mice as models for stroke 
• Animal models for gene therapy of arteriovenous malformations
• Gene transfer to cerebral blood vessels  
• Gene therapy for vasospasm following subarachnoid hemorrhage  
• NOS gene therapy for cerebral vasospasm
• Gene therapy for stroke 
• Gene therapy for stroke using neurotrophic factors
• Gene therapy of strokes with a genetic component
• Gene therapy for intracranial aneurysms 
• RNAi-based gene silencing for neuroprotection in cerebral ischemia  
• Concluding remarks about gene therapy for stroke. 
• Gene therapy of injuries to the nervous system
• Traumatic brain injury  
• Spinal cord injury
• Peripheral nerve injuries
• Gene therapy of epilepsy
• Gene therapy for control of seizures
• Gene therapy for neuroprotection in epilepsy  
• Gene therapy for genetic forms of epilepsy
• Gene therapy for multiple sclerosis
• Gene therapy for impairment of special senses
• Gene therapy for hearing loss 
• Gene therapy for olfactory impairment
• Gene therapy for relief of pain
• Rationale of gene therapy for pain
• Vectors for gene therapy of pain 
• Methods of gene delivery for pain  
• Endogenous analgesic production for cranial neuralgias
• Gene delivery by intrathecal route 
• Gene transfer for delivery of analgesics to the spinal nerve roots  
• Gene therapy of peripheral neuropathic pain  
• Gene transfer by injections into the brain substance 
• Targets for gene therapy of pain 
• Zinc finger DNA-binding protein therapeutic for chronic pain 
• Gene therapy for producing enkephalin to block pain signals 
• Targeting nuclear factor-B  
• Gene therapy targeted to neuroimmune component of chronic pain  
• Potential applications of gene therapy for management of pain  
• Concluding remarks on gene therapy for pain  
• Gene therapy for psychiatric disorders  
• Gene therapy for depression
• Gene therapy for enhancing cognition after stress 
• Gene therapy against fear disorders
• Companies involved in gene therapy of neurological disorders  

7. Gene Therapy of Cardiovascular Disorders

• Introduction  
• Techniques of gene transfer to the cardiovascular system 
• Direct plasmid injection into the myocardium  
• Catheter-based systems for vector delivery
• Ultrasound microbubbles for cardiovascular gene delivery
• Vectors for cardiovascular gene therapy
• AAV vectors for therapeutic delivery to the heart 
• Adenoviral vectors for cardiovascular diseases 
• Molecular cardiac surgery with recirculating delivery of AAV vectors  
• Plasmid DNA-based delivery in cardiovascular disorders
• Gene therapy for counteracting hypoxia in myocardial ischemia
• Therapeutic angiogenesis vs vascular growth factor therapy  
• Gene painting for delivery of targeted gene therapy to the heart
• Gene delivery to vascular endothelium
• Targeted plasmid DNA delivery to the cardiovascular system with nanoparticles  
• Vascular stents for gene delivery
• Gene therapy for genetic cardiovascular disorders 
• Catecholaminergic polymorphic ventricular tachycardia... 
• Genetic disorders predisposing to atherosclerosis
• Familial hypercholesterolemia 
• Apolipoprotein E deficiency 
• Hypertension
• Genetic factors for myocardial infarction
• Acquired cardiovascular diseases  
• Coronary artery disease with angina pectoris
• Ad5FGF-4. 
• Gene therapy for improving long-term CABG patency rates
• Ischemic heart disease with myocardial infarction 
• Gene therapy and angiogenesis in ischemic heart disease 
• Induction of angiogenesis in myocardium by HEXIM1 re-expression  
• Myocardial repair with IGF-1 therapy
• Metalloproteinase-2 inhibitor gene therapy
• miRNA gene therapy for ischemic heart disease  
• Congestive heart failure 
• Rationale of gene therapy in CHF  
• AAV-mediated gene transfer for CHF
• AngioCell gene therapy for CHF 
• β-ARKct gene therapy 
• Elevating cardiac dATP by gene therapy to improve cardiac function  
• Elevating cardiac adenyl cylase type 6 to improve cardiac function 
• Intracoronary adenovirus-mediated gene therapy for CHF 
• nNOS gene transfer in CHF. 
• Cardiomyopathies 
• Cardiac arrhythmias
• Gene transfer approaches for biological pacemakers 
• Genetically engineered biological pacemakers
• Gene therapy for ventricular arrhythmia 
• Gene therapy and heart transplantation  
• Hyperlipidemia and hypercholesterolemia
• Antisense approach to hypertriglyceridemia.. 
• Cholesterol reduction by genetic engineering of PCSK9 gene 
• Inactivating variants in ANGPTL4 for lowering circulating triglycerides
• Peripheral arterial disease
• Incidence and clinical features
• Current management
• Gene therapy for peripheral arterial disease 
• Angiogenesis by gene therapy  
• HIF-1 gene therapy for peripheral arterial disease
• HGF gene therapy for peripheral arterial disease
• Prevention of restenosis after angioplasty
• Antisense approaches  
• Gene therapy to prevent restenosis after angioplasty  
• hTIMP-1 gene therapy to prevent intimal hyperplasia  
• miRNA-based gene therapy for restenosis  
• NOS gene therapy for restenosis
• Techniques of gene therapy for restenosis 
• Maintaining vascular patency after surgery
• Companies involved in gene therapy of cardiovascular diseases
• Future of gene therapy of cardiovascular disorders

8. Gene therapy of viral infections 

• Introduction  
• Acquired Immunodeficiency Syndrome (AIDS)  
• Current management of AIDS 
• Gene therapy strategies in HIV/AIDS  
• Cell/gene therapies for HIV/AIDS
• Anti-HIV ribozyme delivered in hematopoietic progenitor cells  
• Autocrine interferon (INF)- production by somatic cell gene therapy 
• Gene editing for HIV-1
• Transplantation of genetically modified T cells 
• Transplantation of genetically modified hematopoietic cells  
• Inhibition of HIV-1 replication by lentiviral vectors
• VRX496-T  
• Insertion of protective genes into target cells  
• HIV/AIDS vaccines
• Intracellular immunization... 
• Engineered cellular proteins such as soluble CD4s 
• Intracellular antibodies
• Anti-rev single chain antibody fragment  
• Use of genes to chemosensitize HIV-1 infected cells
• Antisense approaches to AIDS
• RNA decoys 
• Antisense oligodeoxynucleotides
• RNA decoys 
• Ribozymes
• RNAi applications in HIV/AIDS
• siRNA-directed inhibition of HIV-1 infection 
• Role of the nef gene during HIV-1 infection and RNAi  
• Bispecific siRNA constructs
• Targeting CXCR4 with siRNAs
• Targeting CCR5 with siRNAs
• Companies involved in developing gene therapy for HIV/AIDS
• Conclusions regarding gene therapy of HIV/AIDS
• Genetic vaccines for other viral infections
• Cytomegalic virus infections  
• Viral hepatitis  
• Vaccine for hepatitis B
• Vaccine for hepatitis C
• Gene therapy for hepatitis C
• Vaccine for herpes simplex virus 
• DNA vaccine against rabies
• DNA vaccine for Ebola  
• Vaccines for avian influenza  
• Future prospects of DNA vaccines for avian influenza  
• Human trial of a DNA vaccine for avian influenza 
• Companies developing genetic vaccines for infections other than AIDS

9. Research, Development and Future of Gene Therapy 

• Basic research in gene therapy  
• R & D in gene therapy 
• Animal models of human diseases for gene therapy research 
• Lentiviral transgenesis
• Financing research and development
• Role of the NIH in gene therapy research 
• National Gene Vector Laboratories
• Funding of gene therapy research in Europe 
• Gene therapy funding in Horizon 2020 of European Commission
• Financing by the industry  
• Clinical trials in gene therapy 
• Clinical trials worldwide 
• Clinical trials in cancer gene therapy
• Trials of gene therapy for neurological disorders
• Clinical trials for genetic disorders
• Clinical trials in cardiovascular gene therapy  
• Clinical trials for infectious diseases
• Gene therapy for other disorders  
• Clinical trials in the US  
• Vectors used in gene therapy clinical trials  
• Vector analytics for clinical trials using rAAV vectors 
• Gene therapy in China 
• Future of gene therapy  
• How to improve gene therapy 
• International Gene Therapy Consortium  
• Future opportunities and challenges for gene therapy
• Promising areas of application of gene therapy 
• Neurological disorders
• Gene therapy of cardiovascular disorders
• Cancer gene therapy
• Personalized gene therapy 

10. Regulatory, Safety, Ethical Patent Issues of Gene Therapy

• Regulation of gene therapy in the United States 
• US Federal guidelines for research involving recombinant DNA molecules
• Regulation of gene therapy in the US
• Implantation of genetically manipulated cells. 
• Modification of oocytes for use in IVF... 
• Clinical trials in gene therapy 
• Gene therapy INDs placed on hold by the FDA
• FDA policy for advancing the development of gene therapy 
• Future for approval of gene therapy in the US 
• Do-it-yourself gene therapy  
• Regulation of gene therapy in Europe 
• European Union
• Regulation of gene therapy in Germany  
• Preclinical research
• Clinical Trials  
• Marketing authorization 
• Regulation of gene therapy in the United Kingdom
• Regulation of gene therapy in France 
• Regulation of gene therapy in Italy 
• Regulation of gene therapy in the Netherlands... 
• Gene therapy regulation in Switzerland. 
• Regulation of gene therapy in Australia
• Regulation of gene therapy in Japan  
• Regulation of gene therapy in China  
• Safety issues of gene transfer
• Adverse effects of retroviral vectors
• Insertional mutagenesis
• Adverse effects of HSV vectors  
• Neurotoxicity of HSV vectors 
• Hepatotoxicity of HSV-tk/ganciclovir approach 
• Adverse effects of adenoviral vectors 
• Inflammatory effects of adenoviruses in lungs 
• Inflammatory effects involving the liver
• Induction of immune response by adenoviral vectors
• Impairment of adrenocortical steroidogenesis
• Adverse effects of AAV vectors
• Toxicity associated with cationic lipid-mediated gene transfer 
• Toxicity of lipopolysaccharides
• Potential side effects of RNAi gene therapy 
• Role of molecular diagnostics in safety of gene therapy 
• Quality control of vectors  
• Testing for retroviruses 
• Adenoviral vectors  
• Replication competent viruses  
• Genetic characteristics of viral vectors 
• Concluding remarks about safety of viral vectors
• Ethical aspects of gene therapy
• The lay consumer's view of somatic gene therapy ethics
• Ethical aspects of clinical trials
• Regulatory and ethical issues for in utero gene therapy 
• Ethical aspects of germline gene therapy 
• Ethical aspects of mitochondrial replacement therapy
• Ethical aspects of gene editing
• Ethical aspects of clinical trials of germline editing  
• Gene editing in the UK
• Gene editing in the US
• Guidelines for gene editing by Alliance for Regenerative Medicine
• UNESCO’s view on gene editing in humans
• Concluding remarks on the ethical aspects of genome editing
• Germline gene therapy for genetic enhancement
• Athletic enhancement by genetic engineering  
• Gene doping in sports  
• Gene transfer methods used for enhancing physical performance  
• Adverse effect of genetic engineering 
• Problems in detecting genetic manipulations in athletes
• Ethical dilemma  
• Gene therapy patents 
• CRISP/Cas9 patents

Tables 
Table 1-1: Landmarks in the development of gene therapy
Table 2-1: Classification of methods of gene therapy
Table 2-2: A comparison of various physical methods of gene transfer
Table 2-3: Experimental applications of gene transfer by electroporation 
Table 2-4: An overview of characteristics of commonly used viral vectors
Table 2-5: Companies using viral vectors 
Table 2-6: Companies using nonviral vectors  
Table 2-7: Target organs for nonviral gene therapy methods.
Table 2-8: CRISPR vs other gene editing tools
Table 2-9: Companies developing CRISPR technology  
Table 2-10: Companies developing CAR-T cell therapy
Table 2-11: Potential routes for administration of DNA
Table 2-12: Companies with gene delivery devices/ technologies
Table 2-13: Strategies for targeted gene therapy  
Table 2-14: Animal experimental studies of in vivo gene delivery with polymer systems
Table 2-15: Approaches to controlling gene expression in gene therapy
Table 2-16: Companies with regulated/targeted gene therapy and special techniques 
Table 2-17: Potential applications of human germline genome modification  
Table 2-18: Applications of molecular diagnostics in gene therapy
Table 2-19: Advantages of gene therapy compared with protein therapy  
Table 3-1: Experimental approaches to gene therapy of rheumatoid arthritis 
Table 3-2: Gene therapy strategies for osteoarthritis 
Table 3-3: Cell and gene therapy approaches for type 1 diabetes mellitus... 
Table 3-4: Indications for gastrointestinal gene therapy
Table 3-5: Hematological disorders that can be potentially treated by gene therapy.  
Table 3-6: Clinical trials of gene therapy for hemophilia A and B  
Table 3-7: Companies involved in gene therapy of hematological disorders
Table 3-8: Techniques of gene transfer to the kidneys 
Table 3-9: Gene therapy in animal experimental models of renal disease.
Table 3-10: Applications of gene therapy in ophthalmological disorders 
Table 3-11: Companies developing gene therapy for eye disorders  
Table 3-12: Strategies for gene delivery to the lungs
Table 3-13: Companies developing gene therapy for pulmonary disorders 
Table 4-1: Genetic disorders that are being investigated for gene therapy 
Table 4-2: X-linked immunodeficiency disorders 
Table 4-3: Examples of inherited metabolic disorders amenable to gene therapy
Table 4-4: Gene therapy approaches to Duchenne muscular dystrophy 
Table 4-5: Companies involved in gene therapy of genetic/metabolic disorders
Table 5-1: Strategies for cancer gene therapy
Table 5-2: Cell-based gene therapy for cancer  
Table 5-3: Companies with nucleic acids/genetically modified cell cancer vaccines
Table 5-4: Enzyme/prodrug combinations employed in suicide gene therapy
Table 5-5: Mutation compensation strategies used clinically 
Table 5-6: Companies developing oncolytic viruses 
Table 5-7: Strategies for gene therapy of malignant brain tumors 
Table 5-8: Clinical trials of oncolytic virotherapy against glioblastoma multiforme  
Table 5-9: Clinical trials of gene therapy in ovarian cancer  
Table 5-10: Gene therapy for malignant melanoma.. 
Table 5-11: Clinical trials of gene therapy for prostate cancer
Table 5-12: Companies involved in cancer gene therapy
Table 6-1: Example of potential indications for gene therapy of neurologic disorder
Table 6-2: Methods of gene transfer as applied to neurologic disorders 
Table 6-3: Gene therapy techniques applicable to Parkinson disease 
Table 6-4: Companies developing gene therapy for Parkinson's disease 
Table 6-5: Gene transfer in animal models of carotid artery restenosis
Table 6-6: Gene therapy strategies for vasospasm
Table 6-7: Neuroprotective gene therapy in animal stroke models
Table 6-8: Experimental gene therapy approaches for relief of pain
Table 6-9: Companies involved in gene therapy of neurological disorders
Table 7-1: Cardiovascular disorders that are potential indications for gene therapy 
Table 7-2: Catheter-based systems for vector delivery to the cardiovascular system  
Table 7-3: Companies involved in gene therapy of cardiovascular diseases
Table 8-1: Strategies for gene therapy of AIDS
Table 8-2: Companies involved in developing gene therapy for HIV/AIDS
Table 8-3: Companies developing genetic vaccines for infections other than AIDS
Table 9-1: Geographical distribution of gene therapy clinical trials
Table 9-2: Opportunities and challenges for gene therapy and resources needed
Table 9-3: Potential applications of gene therapy in disorders of the nervous system
Table 10-1: Genes that may be used for performance enhancement 

Figures 
Figure 1-1: Relation of gene therapy to other biotechnologies
Figure 1-2: Relationship of DNA, RNA and protein in the cell
Figure 2-1: Ex vivo and in vivo techniques of gene therapy
Figure 2-2: Structure of the Helios gene gun
Figure 2-3: Categories of rAAV-based gene therapy strategies  
Figure 2-4: Gene editing by zinc finger nucleases 
Figure 2-5: Genome engineering by transcription-activator–like-effector-nucleases 
Figure 2-6: Mechanism of action of GeneRide technology  
Figure 2-7: A scheme of CRISPR/Cas9 gene editing
Figure 2-8: Use of CRISPR-Cas9 for hereditary hearing loss  
Figure 2-9: Chimeric antigen receptor (CAR)-T cells attacking tumor cells
Figure 2-10: Schematic of suppression of gene expression by RNAi  
Figure 3-1: Retina and routes of administration of gene therapy for retinal disorders
Figure 4-1: Targeted gene correction of α1-antitrypsin deficiency by iPSCs
Figure 4-2: Application of CRISPR-Cas9 in a mouse model of DMD
Figure 4-3: Techniques for mitochondrial nuclear transfer
Figure 5-1: Gene therapy approaches for pancreatic cancer 
Figure 6-1: Effect of tyrosine hydroxylase gene delivery on dopamine levels
Figure 6-2: Role of cell and gene therapy in stroke according to pathology and stage
Figure 9-1: Product development cycle in gene therapy  
Figure 9-2: Proportions of therapeutic areas in clinical trials of gene therapy in the US
Figure 9-3: Proportions of various vectors used in gene therapy trials  

Gene Therapy
Part 2: Markets and Companies

11. Markets for Gene Therapy

• Introduction  
• Approved cell and gene therapy products  
• Gene therapy markets in various regions of the world. 
• Gene therapy markets according to therapeutic areas
• Cancer gene therapy market
• Markets for gene therapy of genetic disorders
• Markets for DNA vaccines  
• DNA vaccines markets according to technologies
• DNA vaccines markets according to therapeutic indications
• DNA vaccines markets according to geographical areas 
• Competing treatments
• Antisense 
• RNAi
• Cell therapy 
• Strategies for developing gene therapy markets
• Collaboration with pharmaceutical companies 
• Collaboration with companies developing cell-based therapies
• Collaboration with academic gene therapy centers
• Developing safer and cost-effective gene medicines
• Intellectual property and commercialization of gene therapy
• Overcoming obstructions to the development of gene therapy
• Unmet needs in gene therapy  
• Promises and challenges for the development of gene therapy
• Development of gene therapy market in China  
• Challenges of developing gene therapy in the USA
• Challenges of developing gene therapy in the European Union

12. Companies involved in Gene Therapy 

• History of commercial development of gene therapy
• Selection of companies and information  
• Supporting services for gene therapy  
• Profiles of Companies  
• Collaborations 

13. References  

Tables 
Table 11-1: Approved cell and gene therapy products 
Table 11-2:Gene therapy market according to regions/countries − 2020 to 2030
Table 11-3: Gene therapy markets according to therapeutic areas − 2020 to 2030
Table 11-4: Cancer gene therapy market according to type of cancer - 2020 to 2030
Table 11-5: Gene therapy market for selected genetic disorders - 2020 to 2030 
Table 11-6: DNA vaccines markets according to technologies - 2020 to 2030 
Table 11-7: DNA vaccines markets according to therapeutic indications - 2020 to 2030  
Table 11-8: DNA vaccines markets according to geographical areas - 2020 to 2030
Table 12-1: 10 major players in gene therapy
Table 12-2: Companies with supporting services for gene therapy
Table 12-3: Collaborations of gene therapy companies

Figures 
Figure 11-1: Unmet needs in gene therapy

Samples