disease targets

Gene Therapy for Acquired Diseases

Gene therapy can also be used to treat life-threatening infections where no other treatment is available. In this case, genetic information is specifically introduced into infected cells with a view to prevent the effective replication of the target pathogen. In this section we describe some of the approaches that have been adopted in the treatment of the most prevalent infectious diseases.

Gene Therapy for Genetic Disorders

In general, genetic disorders are inherited diseases that arise when someone has two dysfunctional copies of a single gene on both of their chromosomes. The result of this is often devastating, resulting in abnormal functioning of specific cells and the development of an often life-threatening condition. In these cases gene therapy is employed to replace the dysfunctional gene with a correct copy and restore the normal functioning of affected cells. In this page we describe some of the most well-known genetic disorders that are being targeted by the gene therapy community.

An Introduction to Cancer Gene Therapy

Cancer can be described as a disease where cellular communication has broken down, allowing transformed cells to escape tight regulatory signals and to replicate autonomously and continously, ultimately invading and interfering with the functions of normal tissues. Under physiological conditions cells communicate with one another by activating receptors at the cell surface, which convey the signal through pathways of proteins located in the cytoplasm and subsequently through networks of transcription factors in the nucleus with control the expression of genes that mediate the cell's response. In this article we briefly describe the gene therapy approaches that have been adopted in an effort to treat cancer.

Typically, cancer develops as a result of aberrant growth factor signalling, where a pathway that instructs a cell to grow and divide becomes constitutively active. This arises through mutations in a growth factor receptor, or through mutations in the components of cell signalling pathways. (Collectively, genes that encode for mutated cellular proteins involved in promoting cell growth are termed oncogenes). Threrefore, in order to effectively treat a cancer, it is essential that all cells that carry a mutated oncogene, are destroyed, otherwise the cancer will continue to grow and spread.

Gene Therapy Strategies for HIV-1 Treatment

Human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS) [1]. According to the report from World Health Organization (WHO), in 2009, there were 33.3 million people living with HIV/AIDS, with 2.6 million new infections and 1.8 million deaths due to AIDS (http://www.who.int/hiv/data/2009_global_summary.png). HIV infection affects a large area and spreads actively ever since it was identified, with a significant number of AIDS deaths occurring in Sub-Saharan Africa [Greener R (2002) AIDS and macroeconomic impact. In S, Forsyth (ed) State of the Art: AIDS and Economics IAEN: pp. 49-55].

Gene Therapy of Ornithine Transcarbamylase Deficiency

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder with an incidence rate of 1:80,000 births in Japan (1). It occurs when a mutant enzyme protein (OTC) impairs the reaction that leads to condensation of carbamoyl phosphate and ornithine to form citrulline. This impairment leads to reduced ammonia incorporation, which, in turn, causes hyperammonemia. Ammonia is especially damaging to the nervous system, so ornithine transcarbamylase deficiency causes neurological problems as well as eventual damage to the liver.

Gene Therapy for Phenylketonuria

PKU is an autosomal recessive disorder resulting from a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH), which converts phenylalanine to tyrosine (figure 1) (1). PAH deficiency is the most common cause of the accumulation of phenylalanine (Phe), called hyperphenylalanemia (HPA), with an incidence of roughly 1:10000 Caucasian live births, with a higher incidence in the populations of Turkey, Ireland and Norway (http://emedicine.medscape.com/article/947781-overview).

Regulation of SOD3 Transgene Expression

A number of different enzymes and molecules are involved in the maintenance of reduction-oxidation reaction (redox) balance in tissues. The three mammalian dismutases, cytosolic CuZnSOD (SOD1), mitochondrial MnSOD (SOD2), and extracellular superoxide dismutase (SOD3) are among the most important redox enzymes. They differ by the cellular localization and therefore have slightly different regulation of expression and therapeutic effects in tissue damage recovery suggesting distinct targets for gene therapy. In the current review I focus on the regulation of SOD3 gene expression in tissues and on the effect of SOD3 transgene on signal transduction.

Targeted Prostate Cancer Gene Therapy

Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in American males today. Novel and effective treatment such as gene therapy is greatly desired. Gene therapy is the direct transfer of DNA into patients’ diseased cells for the purpose of therapy. Viral based gene therapy is to use a genetically-modified, replication defective or so-called cold virus as the gene transfer vehicle. In contrast, nonviral gene therapy is to deliver DNA by nonviral methods. At the current stage, viral gene therapy in general has a much higher gene transfer efficiency in vivo compared to nonviral gene therapy. The early viral-based gene therapy uses tissue-nonspecific promoters, which causes unintended toxicity to other normal tissues. In this mini-review, we will focus on discussion of strategy using transcriptionally-regulated gene therapy strategy for prostate cancer treatment.

A gene therapy cure for ADA-SCID?

A recent article published on the New England Journal of medicine by Aiuti and colleagues reports on the progress of 10 patients that have been treated for ADA-SCID by gene therapy. This is a form of severe combined immuno-deficiency (SCID) where there is a lack of the enzyme adenosine deaminase (ADA), coded for by a gene on chromosome 20.

Gene Therapy for Malignant Pleural Mesothelioma

Mesothelioma is relatively rare in frequency but is one of the intractable cancers linked with asbestos exposure. The patient numbers will increase in near future and current clinical outcomes with conventional treatment modalities are not satisfactory. Gene therapy is a possible therapeutic strategy because of easy accessibility of a vector system into the intrapleural cavity. Several preclinical studies demonstrated that the gene medicine produced anti-tumor effects, suggesting the clinical feasibility. In this review, we summarized the current status of clinical trials targeting mesothelioma.