Gene therapy approach

Although pharmacology still relies heavily on small chemical substances, biologicals like recombinant proteins, cell-based therapies, and gene-therapy approaches have great potential for the treatment of broad spectrum of diseases. Therefore, the focus of modem pharmacology should shift towards these innovative therapies. 

An important safety issue of viral vectors is whether or not the recombinant viruses are able to replicate in the infected cells. Replication of viral vectors is unwanted in most gene-therapy approaches. Therefore, replication-defective vectors have been designed, which are able to perform only one initial infectious cycle within the target cell. In addition, replication-competent vectors have been designed, which are able to productively infect the target cell and to spread in the target tissue. 

Kleimnan et al. 2008). In addition, synthetic siRNAs are also subject to degradation in vivo by nuclease activity. Besides side effects and instability, the efficient and specific delivery of the RNAi indncers to the target cell still requires optimization. Here we snmmarize the cnrrent statns of nncleic acid-based antiviral therapentics. The focns will be on antiviral strategies nsing antisense and RNAi technology. Additionally, antiviral ribozymes and aptamers will be discussed briefly, with a focus on recent studies. Gene therapy approaches and delivery systems are the subject of Chapter 11 of this book. 

Trono D, Feinberg MB, Baltimore D (1989) HlV-1 Gag mutants can dominantly interfere with the replication of the wild-type virus. Cell 59 113-120 Tung FY, Bowen SW (1998) Targeted inhibition of hepatitis B virus gene expression a gene therapy approach. Front Biosci 3 all-al5... 

Table 14.5 Some therapeutic strategies being pursued in an attempt to treat cancer using a gene therapy approach. Refer to text for details...

Caplen, N. 2003. RNAi as a gene therapy approach. Expert Opinion on Biological Therapy 3(4), 575-568. 

Seth P, Katayose D, Li Z, et al. A recombinant adenovirus expressing wild type p53 induces apoptosis in drug-resistant human breast cancer cells a gene therapy approach for drug-resistant cancers. Cancer Gene Ther 1997 4 383-390. 

Antagonists of Receptor Tyrosine Kinases Enhance Therapeutic Response to Radiation Endothelial Repair Gene Therapy Approach to Angiolytic and Angiostatic Therapy in Cancer References... 

GENE THERAPY APPROACH TO ANGIOLYTIC AND ANGIOSTATIC THERAPY IN CANCER... 

A patient with ornithine transcarbamylase (OTC) deficiency is being treated in a gene therapy clinical trial. The gene therapy approach for this disease is primarily designed to... 

Thee future prospects for naked DNA gene therapy include clinical trials for genetic diseases (e.g., Duchenne muscular dystrophy, ischemia, hemophilia), which would be initiated in the next few years, and tail vein injections in rodents, which will become a widely used technique for rapidly testing expression vectors/gene therapy approaches (101). 

Rinsch, C., Regulier, E., Deglon, N., Dalle, B., Beuzard, Y. and Aebischer, P. (1997) A gene therapy approach to regulated delivery of erythropoietin as a function of oxygen tension. Hum. Gene Ther., 8, 1881-1889. 

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). 

Traditional treatment of epilepsy involves anticonvulsants to block excitatory transmission. The majority of these antiepileptic drugs are known ion channel blockers [for a summary see Gourfin-kel-An et al. (2004)] More drastic approaches involve surgical removal of the epileptic foci. Gene therapy approaches attempt to block excitation by blocking gene expression (Xiao et al., 1997 Haberman et al., 2002) of excitatory neurotransmitters or by overexpression of the genes involved in inhibition of excitation (Haberman et al., 2003 Lin et al., 2003 Richichi et al., 2004). 

Xu, F., Ding, E., Liao, S. X., Migone, F., Dai, J., Schneider, A., Serra, D., Chen, Y. T. and Amalfitano, A. (2004). Improved efficacy of gene therapy approaches for Pompe disease using a new, immune-deficient GSD-II mouse model. Gene Ther. 11(21), 1590-1598. 

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