Cell and gene therapy at the dawn of a new era for the effective treatment of a broad spectrum of inherited and acquired disorders.

Ever since the initial transfer of genes to eukaryotic cells and the subsequent birth of “gene therapy”, the field has come a very long way. The initial successes in the treatment of inherited genetic disorders, is now rapidly extending to include potential therapies for a range of non-genetic and common acquired disorders. It is now possible to add or remove one or more specific genes from specific cell or their progeny. In addition, it is also possible to use a variety of strategies based on the use of site specific base excision or targeted endonucleases to achieve exquisite levels of accuracy in the editing of the genome. Furthermore, the better understanding of the steps involved in the regulation of transcription, translation and post-translational modification and processing of gene products, has enabled the introduction of unprecedented levels of control and regulation of gene expression. This has allowed the development of entirely novel strategies not only for the targeted expression of therapeutic genes, but also the auto-regulation, and the induction of intuitive responses to a range of physiological cues. Combined with the targeted delivery of genes to specific subsets of cells, not only in vitro, but in vivo, we are now at the start of a new era in the delivery and expression of therapeutic genes with in-built intuitive and autoregulated responses to changing physiological requirements in specifically targeted tissues in the body. These developments are now heralding major breakthroughs in physiologically appropriate levels of insulin, site specific vasodilation and anti-inflammatory reactions in response to physiological signals.

The very rapid pace of progress in gene therapy, including the clinical application of cell and gene therapy. This has already resulted in the development of new therapies and licensed drug products for a variety of previously untreatable conditions, such as multiply relapsed leukemias, or a whole range of inherited genetic disorders. It is often a surprise to clinical scientists just outside the direct field of cell and gene therapy we can now use components of the regulatory elements such as promoters, enhancers, micro-RNAs, stability and instability sequences (both at the RNA and protein levels), as well as multiple post-translational modifications to achieve highly sensitive and exquisitely responsive regulation of therapeutic genes. An appropriate analogy is the use of only 10 digits, as in the numbers 0 to 9, to generate complex telephone numbers that allow highly specific telephonic connections to be made to any one of billions of people in the world. Conceptually, the control of gene expression can be achieved with many more regulatory components than is available for the construction of telephone numbers! Therefore the generation of highly responsive therapeutic and safety switches, the latter for the control of unwanted side effects, is now entirely possible. The thematic issue will provide highly valuable insights into a rapidly expanding field in biomedical research and development.

Keywords: Gene Therapy, Cell Therapy, Viral Vectors, Non-Viral Vectors, In Vivo Gene Therapy, CAR T Cells, CAR iKT Cells, CAR T cells for leukemia, CAR T cells for solid Cancer, Car T cells for Auto-immune disorders, Cell and Gene Therapy for Cardio Vascular Disease, Autologous, Allogeneic and Universal CAR T cells; Oncolytic Viruses, Measles Virus, Herpes Simplex Virus, Adenovirus, AAV, Reovirus, Newcastle Disease Virus, Poliovirus, Gamma-retrovirus, Non-Integrating Lentivirus, Targeted Delivery of Viral and Non-viral Vectors, Targeted Expression of Therapeutic Genes, Auto-Regulated Vectors, Intuitive Regulation of Gene Expression, Synthetic Vectors and Cells