Gene Therapy

Gene therapy is a therapeutic method for correcting defective genes responsible for disease development. There are several ways to accomplish this task.

First, a normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene.

Secondly, an abnormal gene could be swapped for a normal gene through homologous recombination or the abnormal gene could be repaired through selective reverse mutation, which the gene regains its normal function.

Lastly, the regulation of a particular gene expression could be altered to achieve a therapeutic benefit.

In order to understand the process better please watch the video of gene therapy designed by Fatima Bosch, Carles Roca, Xavier Anguela and Albert Ruzo from the Center for Animal Biotechnology and Gene Therapy of the Universitat Autónoma de Barcelona (UAB). The design of this video has been supported by CliniGene.

Cell Therapy

Cell therapy is defined as the administration of live whole cells or maturation of a specific cell population in a patient for the treatment of a disease.

Compared to Gene Therapy, Cell Therapy is an older discipline, dating back to the first blood transfusions performed in the 1940's, and proceeding through organ and bone marrow transplantation in the 1960s and 70s, to the recent modern adoptive transfer of lymphocytes to treat cancer and the potential to use stem cells to repair damaged organs in the near future.

In most gene therapy studies, a "normal" gene is inserted into the genome to replace an "abnormal," disease-causing gene. A carrier molecule called a vector must be used to deliver the therapeutic gene to the patient's target cells.

Currently, the most common vector is a virus that has been genetically altered to carry normal human DNA. Viruses have evolved a way of encapsulating and delivering their genes to human cells in a delicate manner. Scientists have tried to take advantage of this capability and manipulate the virus genome to remove disease-causing genes and insert therapeutic genes instead.

Target cells such as the patient's liver or lung cells are infected with the viral vector. The vector then unloads its genetic material containing the therapeutic human gene into the target cell. The generation of a functional protein product from the therapeutic gene restores the target cell with a normal function.

Historically, blood transfusions were the first type of cell therapy and are now considered routine. Bone marrow transplantation has also become a well-established protocol. Bone marrow transplantation is the treatment of choice for many kinds of blood disorders, including anemias, leukemias, lymphomas, and rare immunodeficiency diseases.

Cell therapy is expanding its repertoire of cell types for administration. Cell therapy treatment strategies include isolation and transfer of specific stem cell populations, administration of effector cells, induction of mature cells to become pluripotent cells, and reprogramming of mature cells.

Administration of large numbers of effector cells has benefited cancer patients, transplant patients with unresolved infections, and patients with chemically destroyed stem cells in the eye.

Gene therapy and cell therapy are overlapping fields of biomedical research with the goals of repairing the direct cause of genetic diseases in the DNA or cellular population, respectively.

These powerful strategies are also being focused on modulating specific genes and cell subpopulations in acquired diseases in order to reestablish the normal equilibrium. In many diseases, gene and cell therapy are combined in the development of promising therapies.

In addition, these two fields have helped provide reagents, concepts, and techniques that are elucidating the finer points of gene regulation, stem cell lineage, cell-cell interactions, feedback loops, amplification loops, regenerative capacity, and remodeling.

Gene and Cell Therapy in Action

Gene therapy is defined as a set of strategies that modify the expression of an individual's genes or that correct abnormal genes. Each strategy involves the administration of a specific DNA (or RNA).

Cell therapy is defined as the administration of live whole cells or maturation of a specific cell population in a patient for the treatment of a disease.

Gene and Cell Therapy for Diseases

Gene and Cell Therapies have made important medical advances in less than three decades. Within this short time span, both gene and cell therapies have explored multiple concepts, developed various technologies, assessed the advances in different animal models, and tested the novel therapies in multiple human clinical trials of dreaded diseases.

Some exciting improvements have been observed in several diseases by the treatments. Although several trials did not provide the hoped-for-advances, each trial has advanced our understanding of the complex interactions between different tissues and highlighted challenges for further research.

Among the most notable advancements in gene and cell therapies are discussed in the following diseases.

Blood Disorders and Anemias

Blood disorders encompass a wide variety of diseases including anemias, cancer, hemophilias, and immunodeficiencies. Blood disorders include various cancers such as Leukemias, T cell lymphomas, B cell lymphomas, Burkitts Lymphoma, and Hodgkins Disease.

Anemias includes sickle cell anemia, beta and alpha thalassemias, and Fanconi anemia. Patients with anemia have low numbers of red blood cells or abnormal red blood cells. Inherited anemias are caused by a mutation in an essential gene involved in the development, function, or lifespan of the red blood cells or erythrocytes.

The progress and challenges in development of gene and cell therapies for several types of anemia are summarized below.

Blood DisordersClick arrow to

Cancer Gene and Cell Therapy

Approaches to cancer gene therapy include three main strategies: the insertion of a normal gene into cancer cells to replace a mutated gene, genetic modification to silence a mutated gene, and genetic approaches to directly kill the cancer cells.

Furthermore, approaches to cellular cancer therapy currently largely involve the infusion of immune cells designed to either (i) replace most of the patient's own immune system to enhance the immune response to cancer cells, (ii) activate the patient's own immune system (T cells or Natural Killer cells) to kill cancer cells, or (iii) to directly find and kill the cancer cells.

Currently multiple promising clinical trials using these gene and cell based approaches are ongoing in patients with a variety of different types of cancer. The strategies, associated challenges, and clinical trial progress are summarized below.

Gene and Cell Therapy of CancerClick arrow to

Cardiovascular Diseases

Many gene therapy efforts are focusing on treatment of patients with isolated areas of heart damage, since technology to reach all of the cells in the heart is still being developed. Additionally, in most cases of acquired heart disease, injury is restricted to discrete zones.

Cell therapy is also being developed to treat acute cardiac events such as a heart attack and chronic cardiovascular diseases (congestive heart failure, cardiomyopathy, peripheral vascular disease).

The status of the developing gene and cell therapy treatments for cardiovascular diseases are described in greater detail below.

Gene and Cell Therapy of CancerClick arrow to

Congenital Blindness and Eye Diseases

Gene therapy trials for 2 eye diseases, Leber congenital amaurosis (LCA) and Stargardt disease, are ongoing or recently completed. Transplantation of limbal epithelial stem cells for treatment of their deficiency is the first cell therapy for ocular diseases in clinical practice.

Patients enrolled in clinical trials have observed benefits which provide proof of feasibility of treating damaged eyes. Although challenges still exist in the treatment of eye diseases, the improved vision of the treated patients are very encouraging.

Development of gene and cell therapies for eye diseases is a hotly pursued field.

Gene and Cell Therapy of CancerClick arrow to

Type 1 Diabetes

Gene therapy investigators are currently studying approaches to efficiently transfer the insulin gene into other cells such as the liver, stomach, or intestines.

In addition, cell therapy approaches for this disease are focused on developing the most efficient methods for the isolation of pancreas beta cells or appropriate stem cells, appropriate location for cell transplant, and improvement of their survival upon infusion. Alternatively, gene and cell therapy scientists are developing methods to reprogram some of the other cells of the pancreas to secrete insulin.

Currently ongoing clinical trials using these gene and cell therapy strategies hold promise for improved treatments of type I diabetes in the future.

Gene and Cell Therapy of CancerClick arrow to


Several gene and cell therapy strategies are in various stages of development to treat hemophilia. Although gene therapy studies with a specific vector in animals showed long term expression of the relevant clotting factor (Factor VIII or Factor IX), the therapeutic effect in a subsequent human trial was only temporary.

Alternatively, hematopoietic stem cells can be modified by gene therapy in tissue culture to express Factor VIII or Factor IX. Transplantation of these cells into mouse models has resolved the disease, and efforts are underway to extend the approach to the dog model of hemophilia.

In a clinical trial for hemophilia B conducted in the United States, the therapeutic gene (Factor IX) in an adeno-associated viral vector was introduced into the liver of patients. At the highest dose tested, therapeutic levels of the clotting factor were observed in the circulation.

Gene and Cell Therapy of HemophiliaClick arrow to

Immunodeficiency Diseases

Immunodeficiency is a defect in the immune system that prevents immune resistance to infectious disease and some forms of cancer.

There are two types of immunodeficiency: the primary or congenital form, caused by genetic defect in one of several essential genes involved in maturation of the immune response; and the acquired or secondary immunodeficiency caused by chemotherapy, some forms of cancer or chronic infections such as AIDS.

Congenital diseases are caused by a mutation in any one of several genes essential to the development of a fully active immune response. Although congenital immunodeficiency was initially treated by transplantation of allogeneic hematopoietic stem cells, the past 20 years has shown that these conditions are correctable by gene therapy as suggested below.

Gene and Cell Therapy of HemophiliaClick arrow to

Infectious Diseases

Viral infections can be life threatening in patients who are immune-compromised because they cannot mount an effective immune response. Approaches to protection from infection using gene therapy include T cell-based immunotherapy, stem-cell based therapy, genetic vaccines, and other approaches to genetic blockade of infection.

The rationale for use of gene therapy is that most common viral or fungal infections are only life threatening in patients who are immune-compromised because they cannot mount an effective immune response to the virus.

Use of genetic vectors for rapid introduction of protective proteins have been shown to be feasible in animal models as well.

Gene and Cell Therapy of HemophiliaClick arrow to

Lysosomal Storage Diseases

Over the years many cell and gene therapy approaches have been tested in animal models of lysosomal storage diseases, and two main approaches have emerged as the most promising for translation into human clinical trials: In vivo gene transfer by direct infusion of viral vectors (AAV and lentivirus vectors) encoding normal enzymes; or modification of bone marrow stem cells in culture with viral vectors encoding normal enzymes (retrovirus and lentivirus vectors) followed by transplantation (this latter approach is often referred to as ex vivo gene therapy).

For in vivo gene transfer, adeno-associated virus (AAV) and HIV-1-derived lentivirus vectors are the most effective gene delivery vehicles as they are devoid of any viral genes, are capable of infecting dividing and non-dividing cells with no apparent short- or long-term toxicity, and most importantly appear to be capable of directing life-long high-level expression of the recombinant enzymes (in the absence of immunological complications related to expression of normal enzymes in animals where the enzyme is absent entirely).

Gene and Cell Therapy of HemophiliaClick arrow to

Respiratory Diseases

Two genetic diseases of the respiratory tract appear amenable for treatment by gene and cell therapy: cystic fibrosis and alpha1 anti-trypsin deficiency.

The discovery of the CFTR gene ignited high hopes for a rapid cure of cystic fibrosis by gene therapy. Various vectors that express CFTR have been tested in one or more clinical trials, and 20 trials have been completed to date. Although the recent clinical trials have demonstrated safety in the treated patients, minimal efficacy was evident.

A phase II trial is assessing the safety profile and efficacy of intramuscularly administering an AAV1 vector that carries the alpha1 anti-trypsin gene to patients with alpha1 anti-trypsin deficiency. The results from this and previous trials are helping to develop a gene therapy treatment for patients with severe alpha1 anti-trypsin deficiency.

Gene and Cell Therapy of HemophiliaClick arrow to

Current Status of Gene Therapy Products in USA:

Currently there are no US FDA approved (i.e. FDA licensed) gene therapy products. Gene therapy products are still in the investigational stage, which means that the products are still being studied to assess their safety and efficacy.

Gene therapy products must go through the same rigorous testing that all drugs go through before they are licensed by the FDA. Promising treatments that are not yet licensed are generally only available through a clinical trial. Please visit Turkish Society of Gene and Cell Therapy website in order to get the most recent news on gene and cell Therapy.



Gendicine is a recombinant adenovirus engineered to express wt-p53. This virus is designed to treat patients with tumors which have mutated p53 genes.

Gendicine is the first gene therapy product approved for clinical use in humans. It is manufactured by Shenzhen SiBiono GeneTech.

Gendicine was approved by the Chinese State Food and Drug Administration to treat head and neck squamous cell carcinoma and various forms of cancer.

Rexin G

Rexin G

Rexin-G is a replication-incompetent retroviral vector encoding a dominant-negative mutant form of the human cyclin G1 gene which is designed to interfere with the progression of cell cycle causing cell death via apoptosis-mediated pathways

Cyclin G


The lipid envelope-cloaked nanoparticles 100 nm in diameter

Virtually invisible to the patient's immune system,

Repeated intravenous infusions without unwanted side- effects, Therapeutic gene delivery only to proliferative cells,

Effectively destroys the target cells by way of cytocidal gene delivery thereby eliminating the risk of insertional mutagenesis,

Pathotropic (disease seeking) targeting



Oncorine - the first commerical oncolytic virus product receiving NDA approval by The Chinese SFDA in 2006, for nasopharyngeal carcinoma in combination with chemotherapy.

H-101 is a gene-engineered adenovirus, which selectively replicates in cancer cells. The deletion of early parts of the gene (E1B-55 and E3) allows the virus to induce only the lyses of tumor cell and not normal cell.

Rexin G

Rexin G

These therapeutic nanoparticles seek out and accumulate in cancerous tissues naturally exposing collagenous proteins on surface.i

pathotropic targeting

Images are from Gordon and Hall, Expert Opin. Biol. Ther. (2010) 10(5)


Rexin-G has achieved regulatory approval in the Philippines for the treatment of all chemo- resistant solid tumors, and is approaching regulatory approval in the USA for pancreatic cancer, osteosarcoma, and soft tissue sarcomas, where it has been granted FDA Fast Track designation and Orphan Drug status, respectively.