Nucleic acid therapies ribozymes

The development of nucleic acid-based therapeutics is not as straightforward as researchers had initially anticipated. Stability, toxicity, specificity, and delivery of the compounds continue to be challenging issues that need further optimization. In recent years, researchers have come up with intricate solutions that have greatly improved the efficacy of potential antisense, ribozyme, as well as RNAi-based therapeutics. Clinical trials for all these types of nucleic acid-based therapeutics are underway. So far, data from several trials and studies in animal models look promising, in particular, the therapies that trigger the RNAi pathway. However, history has shown that compounds that do well in phase I or phase II clinical trials may still fail in phase III. A striking example is the nonspecific suppression of angiogenesis by siRNA via toII-Iike receptor 3 (Kleinman et al. 2008). It will become clear in the near future which compounds will make it as a new class of antiviral therapeutics. 

Worldwide on-going work in the field of nucleic acid-based gene therapy targets the question of the delivery, transport, and in-vivo activity of nucleic acid drugs. The results obtained from these studies will be taken into consideration for the in-vivo design of twin ribozymes after the in-vitro assay has proven successful. 

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... 

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