Genetic disease, gene therapy

Disease Cures. Genetic engineering made it possible to develop gene therapy. Genetic diseases are inherited conditions that occur because of one or more genetic changes or mutations that prevent... 

Other promoters that may be useful for the design of targeted vectors are those induced by disease-specific conditions, such as hypoxia (see Table 1). Thus, a promoter responding to hypoxia through activation by the hypoxia-inducible factor-1 (HIF-1) has been successfully used for experimental cancer gene therapy [69], Disease-specific conditions in tumor cells can also directly result from genetic alterations or from altered signaling pathways. The latter are presumably... 

Alveoli represent the primary site for gas exchange within the lung, and thus their health is vital for survival. Alveolar conditions with a primary genetic cause, such as surfactant protein-B (SP-B) deficiency and SP-C deficiency, are prime candidates for a rAAV-gene therapy approach. Diseases in which alveoli are damaged secondary to other defects might also be treated with gene transfer. Such conditions include environmental toxin exposure, infectious diseases, and adult respiratory distress syndrome (ARDS) (Table 4.1) (Rolls et al., 1997, 1998, 2001 Cheers et al 1999 Ruan et al., 2002). 

Karpati, G., Ascadi, G. (1993). The potential for gene therapy in Ducheiuie muscular dystrophy and other genetic muscle diseases. Muscle Nerve 16, 1141-1153. 

An additional consideration that may influence the protocol used is the desired duration of subsequent expression of the gene product. In most cases of genetic disease, long-term expression of the inserted gene would be required. In other instances (e.g. some forms of cancer therapy or the use of gene therapy to deliver a DNA-based vaccine), short-term expression of the gene introduced would be sufficient/desirable. 

Although simple in concept, the application of gene therapy to treat/cure genetic diseases has, thus far, made little impact in practice. The slow progress in this regard is likely due to a number of factors. These include ... 

Another early genetic disease for correction by gene therapy was SCID. One form of this disease is caused by a lack of adenosine deaminase (ADA) activity. ADA is an enzyme that plays a central role in the degradation of purine nucleosides (it catalyses the removal of ammonia from adenosine, forming inosine, which, in turn, is usually eventually converted to uric acid). This leads to T- and B-lymphocyte dysfunction. Lack of an effective immune system means that SCID sufferers must be kept in an essentially sterile environment. 

DNA plasmid-based treatment ( gene therapy ) is considered an alternative to the one based on classical chemical drugs or proteins recovered from recombinant cells. Treatment of acquired and inherent genetic diseases as well as the use of DNA for the purpose of vaccination are potential applications of plasmid DNA (pDNA). The plasmid carries information that allows protein expression in the targeted human cells as well as eukaryotic regulatory elements and specific prokaryotic sequences that control replication in the host cell, see Fig. 10. Formulation is required for ex- or in-vivo administration. Selected systems for gene expression can be viral or non-viral. 

Friedmann T, Roblin R. Gene therapy for human genetic disease. Science 1972 175(25) 949-955. 

In this chapter, we review some of the practical clinical applications of genetic research. Once a gene is identified, it becomes feasible to diagnose the associate genetic disease in at-risk individuals. In addition, gene therapy, the correction of mutations in cells, becomes a possibility. 

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