Anti-sense therapy

Other approaches directed to the mRNA of tyrosine kinase and thereby interfering with their translation to proteins, such as anti-sense therapy and RNA interference (RNAi) are less advanced and currently limited to laboratory studies. 

Kipshidze N, Moses J, Shankar LR, etal. Perspectives on anti-sense therapy for the prevention of restenosis. Curr Opin Mol Ther200l 3 265-277. 

First, we will briefly review the different aspects that are of importance in the use of anti-sense for in vivo therapy. Second, we will describe the effects of antisense targeting to the proximal tubule of the kidney that have been obtained so far. 

Decreased CRH neurotransmission has been studied by administering anti-sense oligodeoxynucleotides corresponding to the start-coding region of CRH mRNA. The application of this kind of gene therapy to stressed rats produced... 

This review will not include immunological approaches to therapy, nor will it include any discussion of gene engineering, or the potential use of anti-sense oligonucleotides. 

Gene therapy — PNA has been used to manipulate gene expression in disease models by a variety of techniques including anti-sense, anti-gene, and transcription factor decoy approaches (6). 

Dritschilo, A., Huang, C.H., Rudin, C.M., Marshall, J., Collins, B., Dul, J.L., Zhang, C., Kumar, D., Gokhale, PC., Ahmad, A., Ahmad, I., Sherman, J.W., and Kasid, U.N. (2006) Phase I study of liposome-encapsulated c-raf anti-sense oligodeoxyribonucleotide infusion in combination with radiation therapy in patients with advanced malignancies. Clin. Cancer Res. 12, 1251-1259. 

The question whether toxins can be used to translocate nucleic acids into cells is very interesting, but this has not been tested seriously up to now. Toxins are interesting candidates for delivery of anti-sense RNA, ribozymes and genes for transformation and gene therapy. So far there is not convincing evidence that toxins have been effective for such purposes. From what is now known about the translocation of diphtheria toxin, it is likely that the nucleic acid would have to be linked end-to-end to the N-terminus of the A-fragment of this... 

The recently completed sequencing of the human genome has demonstrated the presence of a vast number of targets for antisense ohgonucleotides. So we now have thousands of targets, hundreds of preclinical animal studies, and some 20 chnical trials ongoing. Any successful trial with an anti-sense compound will open a floodgate of new therapies for a panoply of diseases. 

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