+353-1-416-8900REST OF WORLD
+44-20-3973-8888REST OF WORLD
1-917-300-0470EAST COAST U.S
1-800-526-8630U.S. (TOLL FREE)

Gene Therapy - Technologies, Markets & Companies

  • PDF Icon


  • 802 Pages
  • November 2021
  • Region: Global
  • Jain PharmaBiotech
  • ID: 4748173

Gene therapy can be broadly defined as the transfer of defined genetic material to specific target cells of a patient for the ultimate purpose of preventing or altering a particular disease state. Genes and DNA are now being introduced without the use of vectors and various techniques are being used to modify the function of genes in vivo without gene transfer. If one adds to this cell therapy particularly with the use of genetically modified cells, the scope of gene therapy becomes much broader. Gene therapy can now be combined with antisense techniques such as RNA interference (RNAi), further increasing the therapeutic applications. This report takes a broad overview of gene therapy and is the most up-to-date presentation from the author on this topic built-up from a series of gene therapy reports written by him during the past decade including a textbook on gene therapy and a book on gene therapy companies. This report describes the setbacks of gene therapy and renewed interest in the topic

Gene therapy technologies are described in detail including viral vectors, nonviral vectors and cell therapy with genetically modified vectors. Gene therapy is an excellent method of drug delivery and various routes of administration as well as targeted gene therapy are described. There is an introduction to technologies for gene suppression as well as molecular diagnostics to detect and monitor gene expression. Gene editing technologies such as CRISPR-Cas9 and CAR-T cell therapies are also included

Clinical applications of gene therapy are extensive and cover most systems and their disorders. Full chapters are devoted to genetic syndromes, cancer, cardiovascular diseases, neurological disorders and viral infections with emphasis on AIDS. Applications of gene therapy in veterinary medicine, particularly for treating cats and dogs, are included.

Research and development is in progress in both the academic and the industrial sectors. The National Institutes of Health (NIH) of the US is playing an important part. As of 2021, over 2050 clinical trials were completed, were ongoing or had been approved worldwide. A breakdown of these trials is shown according to the geographical areas and applications.

Since the death of Jesse Gelsinger in the US following a gene therapy treatment, the FDA has further tightened the regulatory control on gene therapy. A further setback was the reports of leukemia following the use of retroviral vectors in successful gene therapy for adenosine deaminase deficiency. Several clinical trials were put on hold and many have resumed now. Four gene medicines have been approved by the FDA. The report also discusses the adverse effects of various vectors, safety regulations and ethical aspects of gene therapy including gene editing and germline gene therapy.

The markets for gene therapy have been difficult to estimate as there are only a few approved gene therapy products Gene therapy markets are estimated for the years 2020-2030. The estimates are based on epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright. The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets

The voluminous literature on gene therapy was reviewed and selected 750 references are appended in the bibliography. The references are constantly updated. The text is supplemented with 80 tables and 25 figures.

Profiles of 205 companies involved in developing gene therapy are presented along with 270 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold in 2 decades. These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report. John Wiley & Sons published the book in 2000 and from 2001 to 2003, updated versions of these companies (approximately 160 at mid-2003) were available on Wiley's website. Since that free service was discontinued and the rights reverted to the author, this report remains the only authorized continuously updated version on gene therapy companies.

Benefits of this report

  • Up-to-date on-stop information on gene therapy with 79 tables and 25 figures
  • Evaluation of gene therapy technologies
  • 750 selected references from the literature
  • Estimates of gene therapy markets from 2020-2030
  • Profiles of 204 companies involved and collaborations in this area

Who should read this report?

  • Biotechnology companies developing gene therapy
  • Academic institutions doing research in gene therapy
  • Drug delivery companies
  • Pharmaceutical companies interested in gene therapy
  • Gene therapy companies
  • Venture capital and investment companies

The report contains information on the following:

  • Introduction
  • Gene Therapy Technologies
  • Clinical Applications of Gene Therapy
  • Gene Therapy of Genetic Disorders
  • Gene Therapy of Cancer
  • Gene Therapy of Neurological Disorders
  • Gene Therapy of Cardiovascular Disorders
  • Gene therapy of viral infections
  • Research, Development and Future of Gene Therapy
  • Regulatory, Safety and Ethical Issues of Gene Therapy
  • Markets for Gene Therapy
  • References
  • Gene Therapy 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 
  • 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 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

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 

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  

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

Figure 11-1: Unmet needs in gene therapy