13^th International Conference and Exhibition on Advanced Cell and Gene Therapy February 20-21, 2023 Madrid, Spain

Gene Therapy basically involves the introduction or alteration of genetic material within a cell or organism with an intention of curing the disease. Both cell therapy and gene therapy are overlapping fields of biomedical research with the goals of repairing the direct cause of Genetic diseases in DNA or cellular population respectively, the discovery of recombinant DNA technology in the 1970s provided tools to efficiently develop gene therapy. Scientists use these techniques to readily manipulate viral genomes, isolate genes and identify mutations involved in human disease, characterize and regulate gene expressions, and engineer various viral and non-viral vectors. Various long-term treatments for anaemia, haemophilia, cystic fibrosis, muscular dystrophy, Gauscher’s disease, lysosomal storage diseases, cardiovascular diseases, diabetes and diseases of bones and joints are resolved through successful gene therapy and are elusive toda

Cell Therapy is defined as the therapy in which cellular material is injected into a patient in order to recover the healthy tissue. Cell therapy is targeted at many clinical indications in multiple organs by means of several modes of cell delivery. Stem-Cell Therapy is the use of stem cells to treat or prevent a disease or condition. Stem cells are a class of undifferentiated cells which are able to differentiate into required or specialized cell types. Adult or somatic stem cells exist throughout the body after embryonic development and are found available inside the different types of tissue. The stem cell methodology includes the phases of Stem cell or progenitor cell engraftment, differentiation followed by long term replacement of damaged tissue.

In stem cell transplants, stem cells replace cells damaged by chemotherapy or disease or serve as a way for the donor's immune system to fight some types of cancer and blood-related diseases, such as leukemia, lymphoma, neuroblastoma and multiple myeloma. These transplants use adult stem cells or umbilical cord blood.

Classical methods of gene therapy include transfection. It became inefficient and limited mainly due to delivery of gene into actively proliferating cells invitro. Gene therapy utilizes the delivery of DNA into cells by means of vectors such as biological nanoparticles or viral vectors and non-viral methods. The Several kinds of viruses vectors used in gene therapy are retrovirus, adenovirus, adeno-associated virus and herpes simplex virus. While other recombinant viral vector systems have been developed, retroviral vectors remain the most popular vector system for gene therapy protocols and widest application due to their historical significance as the first vectors developed for efficient Gene Therapy application and the infancy of the field of Gene Therapy

A Stem-Cell line is a group of undifferentiated stem cells which is cultured invitro and can be propagated indefinitely. While stem cells can propagate indefinitely in culture due to their inherent cellular properties, immortalized cells would not normally divide indefinitely but have gained this ability to sustain due to mutation. The Immortalized cell lines can be generated from cells by means of isolating cells from tumors or induce mutations to make the cells immortal. An immortalised cell line is a population of multicellular organism cells which has not proliferates indefinitely. Due to mutation, the cells evaded normal cellular senescence and instead undergoing continuous cell division. A key factor in reducing the production costs of biopharmaceuticals is the development of cell lines which in turn produce a high yield of product.

Gene Therapy is used to treat inherited Muscular disorder, cardiovascular disorder, HIV, cancer etc. In stem cell transplants, stem cells replace cells damaged by chemotherapy or disease or as a way for the donor's immune system to provoke immunity against some types of cancer and blood-related diseases, such as leukaemia. Cellular Therapy is internationally recognized for its novel approaches in treating blood related disorders like leukaemia, lymphoma, myeloma, and other life-threatening diseases. The stem cell transplantation of hematopoietic stem cells (HSCT) in which the allogeneic hematopoietic stem cells are harvested from healthy donors of same species and autologous stem cell from the patient itself. Both therapies use high dosage cytotoxic medication in order to induce higher remission rates against malignant diseases. Autologous HSCT preferably used in relapsed malignant high-grade lymphoma and Allogeneic HSCT preferred for therapeutic effect against acute leukaemia with unfavourable prognosis in a high percentage of patients. The Recent developments based on the expansion of the donor pool for allogeneic stem cells in order to reduce dosage as well as chemotherapeutic toxicity of allogeneic transplantation with sustainable anti-leukaemia efficacy.

Regenerative Medicine is the branch of translational research deals with the process of replacing, engineering or regenerating human cells, tissues or organs in order to restore or establish normal functionality of cell. Regenerative medicine is the combination of   tissue engineering and Molecular Biology. Cell Therapy mediate cell repair via five primary mechanisms:  providing an anti-inflammatory effect, homing to damaged tissues and recruiting other cells, such as endothelial progenitor cells for necessary tissue growth, supporting tissue remodelling over scar formation, inhibiting apoptosis programmable cell death, and differentiating tissues into bone, cartilage, tendon, and ligament tissue

The extract derived from the plant cell culture technology is being harnessed and utilized as an active ingredient in anti-aging skincare products. In recent years, researchers have identified naturally occurring botanicals with substantial antioxidant activity proven to protect skin stem cells from UV-induced oxidative stress, inhibit inflammation, neutralize free radicals and reverse the effects of photo aging by means of anti-oxidant activity. Consequently, cosmeceutical products containing plant stem cell derived extracts have the ability to promote healthy cell proliferation and protect against UV-induced dermatological cellular damage in humans. In contrast to epidermal stem cells, plant stem cells are totipotent that they are capable of regenerating an entirely new, whole plant. Through innovative plant stem cell technology, scientists are able to extract tissue from botanicals and regenerate stem cells can be harnessed for use in humans. The use of stem cells derived from botanicals plant, rather than human stem cells, avoids the controversy surrounding the source or methods of extraction of human stem cells while still harnessing the potential of these intriguing cells and its effect in anti-photo aging.

Epigenetics refers to changes in a chromosome which has influence on gene activity and expression. It is also used to describe any heritable phenotypic change that doesn't derive from a modification of the genome, such as prions. Epigenetics is the mechanism for storing and perpetuating or continuing indefinitely a “memory” at the cellular level. The basic molecular epigenetic mechanisms that are widely studied at present – regulation of chromatin structure of cell through histone post-translational modifications and covalent modification of DNA principally through the method of DNA methylation. Chromatin is a dynamic structure that integrates potentially hundreds of signals from the cell surface and has effects of coordinated and appropriate transcriptional response in cell. It is increasingly clear that epigenetic marking of chromatin and DNA itself is an important component of the cell signal integration of entire function that is performed by the genome. Moreover, the changes in the epigenetic state of chromatin in cell can have lasting effects on behavioural changes

Tissue Engineering or Bioengineering is the combinational usage of cells, Engineering, materials methods, suitable biochemical and physicochemical factors in order to improve or replace the infected biological tissues. The field includes the development  of  materials, devices,  techniques to detect and  differentiate disease states ,the treatment response, aid tissue healing, precisely deliver treatments to tissues or cells, signal early changes in health status, and provide implantable bio artificial replacement organs for recover or establish of healthy tissue .Techniques developed here identify and detect biomarkers of disease sub-types, progression, and treatment response, from tissue imaging to genetic testing and Single cell analysis, that aid the more rapid development of new treatments and guide their clinical applications in treating the disorder. It includes the usage of computational modelling, bioinformatics, and quantitative pharmacology to integrate data from diverse experimental and clinical sources to discover new drugs and specific drug targets, as well as to design more efficient and informative preclinical, clinical safety and efficacy studies.

Clinical Trials of Cell and Gene Therapy products often varying from the clinical trials design for other types of pharmaceutical products. This differences in trial design are necessitated by the distinctive features of these products. The clinical trials also reflect previous clinical experience and evidence of medicine. Early experiences with Cell and Gene Therapy products indicate that some CGT products may pose substantial risks to subjects due to effect at cellular and genetic level. The design of early-phase clinical trials of Cell and Gene Therapy products often involves the following consideration of clinical safety issues, preclinical issues, and chemistry, manufacturing and controls (CMC) issues that are encountered.

Diseases can be treated using viruses as vector to deliver genes in Gene Therapy. Viruses as gene vector, however, can themselves cause problems in that they may initiate inflammation and the genes may be expressed at too high a level or for too long period of exposure. The goal of Nano Technology in gene therapy is delivery of therapeutic genes without a virus, using nanoparticles as non-viral vector to deliver the genes.  The particles can be made with multiple layers so the outer layer with covering of peptide that can target the particles to cells of interest at specific site. The emergent Nanotechnology in gene therapy is used to develop unique approaches in treating the retinopathies and the development of micro and Nano dimensional artificial antigen presenting cells (aAPCs) for cancer immunotherapy. These aAPCs mimic the natural signals in immunity that killer T-cells receive when there is an invader (bacteria, virus, cancer cell, etc.) in the body.

Genome editing with engineered nucleases (GEEN) is emergent type of Genetic Engineering. GEEN is the technology in which DNA is inserted, deleted or replaced in the genome. The emergence of highly versatile genome-editing technologies has provided investigators with the ability to rapidly and economically introduce sequence-specific modifications into the genomes of a broad spectrum of cell types and organisms. It also promotes various changes in sub cellular level. Genome Editing itself also holds tremendous potential for treating the underlying various idiopathic genetic causes of certain diseases. The core technologies now most commonly used techniques to facilitate genome editing are clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), zinc-finger nucleases (ZFNs), and homing endonucleases or mega nucleases.

Functionality of biomaterials for these forms is depends upon the chemical reaction such as localized or systemic response at the surface tethered moieties or encapsulated therapeutic factors such as drugs, genes, cells, growth factors, hormones and other active agents to specific target sites. The application of functional biomaterials is rehabilitation, reconstruction, regeneration, repair, ophthalmic applications and act as therapeutic solutions. It has the property of biocompatibility and produce inertness response to the tissue.   The biomaterial-mediated gene therapy aim to use polymeric gene therapy systems to halt the progression of neuron loss through neuroprotective routes and it combine stem cell therapy and biomaterial delivery system in order to enhance regeneration or repair after ischemic injury.

Genetics in Health and Disease in which therapy utilizes genetics, imaging and biological indicators to understand predisposition to disease, what constitutes health during childhood and throughout the life course. Gene and Protein Function are used to develop tools, skills and resources to elucidate gene function and to inform development of new therapies using state-of the-art technologies. Personalised Medicine and Patient benefit is considered to ensure basic science discoveries of disease mechanisms and patient’s genomes are used to produce best effect to improve patients’ lives which include better diagnostics, identification of biomarkers and targeting of therapies.

The global market for cell and gene-based therapies is expected to surpass the $20 billion USD mark by 2025, with an annual growth rate of 21%. The main targets for cell – based therapies are high impact disease areas with significant incurable needs, including cancer, heart disease, neurodegenerative diseases, musculoskeletal disorders and autoimmune diseases. Gene therapies should then not be rushed to market, but companies should gather the required data about the impact of therapy in human community with the appropriate duration of follow-up to allow proper evaluation by payers. In addition, it is key to think about potential reimbursement of the techniques and also the pricing strategies, including risk sharing, as soon as the early clinical development phase

Cardiovascular diseases have become an increasing clinical issue globally. A new challenge in the treatment of the cardiovascular disease is cellular transplantation or cellular cardiomyopathy. Acute ischaemic injury and chronic cardiomyopathies lead to permanent loss of cardiac tissue and ultimately heart failure. Current therapies wide aim to attenuate the pathological changes that occur when injury and to scale back risk factors of vas diseases. However, they do not improve the patient's quality of life or the prognosis more than moderate. Different types of stem cells have been used for Stem Cell Therapy.

The enormous number of companies involved in Cell Therapy has increased progression remarkably during the past few years. More than 500 companies have been identified to be involved in cell therapy and 305 of these are profiled 291 alliances. Of these companies, 170 are involved in stem cells. The Profiles of 72 academic institutions in the US involved in cell therapy along with their commercial collaborations. Allogeneic technology with more than 350 clinical trials is poised to dominate the commercialization of cell therapies in market. Further RandD in cell and gene therapy is expected to bloom given the biologically based advantages.

Cell therapy products require a variety of safety considerations. Stem cell and gene products are heterogeneous substances. There are several areas that particularly need to be addressed as it is quite different from that of pharmaceuticals. These range from creating batch consistency, product stability to product safety, strength and efficacy through pre-clinical, clinical studies and marketing authorization. This review summarizes the existing regulations/guidelines in US, EU, India, and the associated challenges in developing SCBP with emphasis on clinical aspect.