The game-changing role of CRISPR/Cas for genome editing draw interest to programmable RNA-guided tools in general. Currently, we see a wave of papers pioneering the CRISPR/Cas system for RNA targeting, and applying them for site-directed RNA editing. Here, we exemplarily compare three recent RNA editing strategies that rely on three distinct RNA targeting mechanisms. We conclude that the CRISPR/Cas system seems not generally superior to other RNA targeting strategies in solving the most pressing problem in the RNA editing field, which is to obtain high efficiency in combination with high specificity. However, once achieved, RNA editing promises to complement or even outcompete DNA editing approaches in therapy, and also in some fields of basic research.

Inosine (6-deaminated adenosine) is a characteristic modified nucleoside that is found at the first anticodon position (position 34) of several tRNAs of eukaryotic and eubacterial origins, while N1-methylinosine is found exclusively at position 37 (3\' adjacent to the anticodon) of eukaryotic tRNA(Ala) and at position 57 (in the middle of the psi loop) of several tRNAs from halophilic and thermophilic archaebacteria. Inosine has also been recently found in double-stranded RNA, mRNA and viral RNAs. As for all other modified nucleosides in RNAs, formation of inosine and inosine derivative in these RNA is catalysed by specific enzymes acting after transcription of the RNA genes. Using recombinant tRNAs and T7-runoff transcripts of several tRNA genes as substrates, we have studied the mechanism and specificity of tRNA-inosine-forming enzymes. The results show that inosine-34 and inosine-37 in tRNAs are both synthesised by a hydrolytic deamination-type reaction, catalysed by distinct tRNA:adenosine deaminases. Recognition of tRNA substrates by the deaminases does not strictly depend on a particular \"identity\' nucleotide. However, the efficiency of adenosine to inosine conversion depends on the nucleotides composition of the anticodon loop and the proximal stem as well as on 3D-architecture of the tRNA. In eukaryotic tRNA(Ala), N1-methylinosine-37 is formed from inosine-37 by a specific SAM-dependent methylase, while in the case of N1-methylinosine-57 in archaeal tRNAs, methylation of adenosine-57 into N1-methyladenosine-57 occurs before the deamination process. The T psi-branch of fragmented tRNA is the minimalist substrate for the N1-methylinosine-57 forming enzymes. Inosine-34 and N1-methylinosine-37 in human tRNA(Ala) are targets for specific autoantibodies which are present in the serum of patients with inflammatory muscle disease of the PL-12 polymyositis type. Here we discuss the mechanism, specificity and general properties of the recently discovered RNA:adenosine deaminases/editases acting on double-stranded RNA, intron-containing mRNA and viral RNA in relation to those of the deaminases acting on tRNAs.

All Phase II studies with diglycoaldehyde with leukemia and solid tumors have been reviewed. The dose schedules employed ranged from 1.5 to 2.0 g/m2/day for 3 to 5 days. The most common side effects have been gastrointestinal (nausea and vomiting), which occurred in 22% of the patients. Renal toxicity (rise in BUN, creatinine, and urinary proteins) was seem in 17% of the patients treated. Other infrequent toxicities include hypocalcemia (9%) and local complications such as phlebitis. Leukopenia, thrombocytopenia, positive Coombs\' test and impairment in coagulation profile were also reported. In contrast to the hints of therapeutic efficacy described during Phase I trials, in phase II trials no activity was noted among 96 patients with solid tumors and only minimal antileukemic action among 49 other patients. These disappointing Phase II trials coupled with prominent toxicities have prompted the decision to terminate further clinical testing. This report summarizes all clinical observations as an example of circumstances which curtail clinical testing of anticancer drugs.

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A considerable amount of information has accumulated during the past 10 years in the search for antiviral agents. Ribavirin and inosiplex are 2 interesting developments to come out of this search. Ribavirin, a synthetic nucleoside, has an unusually wide spectrum of antiviral activity, especially when tested in vitro. A large number of RNA and DNA viruses are sensitive, especially herpes viruses, poxvirus, influenza, parainfluenza, reovirus, togavirus, and RNA tumour viruses. The in vivo antiviral spectrum of activity is much narrower, with activity against herpes virus, influenza, parainfluenza, measles and adenoviruses. However, controlled clinical trials have not been uniformly successful in treating influenza, hepatitis, herpes simplex and herpes zoster. Inosiplex has been shown to have antiviral activity in vivo against influenza, herpes simplex, rhinovirus and vaccinia virus infections. However, antiviral activity has not been consistently demonstrated, and this observation led to further studies which revealed its immunomodulating effects. The accumulated evidence has indicated that inosiplex is more a prohost agent rather than an antiviral drug. Immune functions which are depressed during viral infection can be restored to normal by inosiplex therapy. At present, neither ribavirin nor inosiplex alone has been shown to be uniformly successful in the treatment of human viral diseases. Nevertheless, their potential place in chemotherapy should not be neglected, although further data are needed to determine what this place will be. Whether combining them with other antiviral agents such as interferon, acyclovir, Ara-A, and so on, would produce a potentiation of action and improved antiviral chemotherapy, will be an interesting area for further study.

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Inosine pranobex is a synthetic compound formed from the p-acetamido benzoate salt of N-N dimethylamino-2-propanol and inosine in a 3:1 molar ratio. It has been reported to exert antiviral and antitumour activities in vivo which are secondary to an immunomodulating effect, and early results suggest beneficial clinical effects in several diseases and infections including mucocutaneous Herpes simplex infections, subacute sclerosing panencephalitis, genital warts, influenza, zoster, and type B viral hepatitis, as well as in homosexual men with persistent generalised lymphadenopathy. However, many of the studies have been preliminary in nature and deficient in design or in the reporting of their results. One must therefore conclude that while inosine pranobex may prove to be a valuable and innovative therapy for a number of diseases and infections for which no satisfactory therapy exist, further long term well controlled studies in larger numbers of patients are required before definitive conclusions about the efficacy of inosine pranobex in these disorders will be possible.