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Adenosine-to-inosine (A-to-I) RNA editing mediated by the ADAR (adenosine deaminase acting on RNA) protein family is the primary type of epitranscriptomic modification known to occur in mammal cells. Recently, several technologies have been developed to re-target this RNA modification to desired locations within specific transcripts. This possibility opened a scenario in which targeted RNA-base editing tools can be used as therapeutic strategies to correct mutations at the RNA level. The chapter will go into detail about the therapeutic potentials of these different RNA base-editing technologies, after providing a brief overview of the roles and functions of ADAR family members. The chapter aims to review the recent advancements of targeted RNA-base editing methodologies and their translation to therapeutic settings. We will discuss strategies leveraging exogenous and endogenous ADAR to create a wholesome perspective on the potential of this molecular mechanism as a tool to correct disease-causing G-to-A point mutations. In this context, clinically relevant approaches and their potential future applications, as well as their currently challenging limitations, will be evaluated.

RNA editing is an epitranscriptomic modification of emerging relevance to disease development and manifestations. ADAR1, which resides on human chromosome 1q21, is an RNA editor whose over-expression, either by interferon (IFN) induction or through gene amplification, is associated with increased editing and poor outcomes in Multiple Myeloma (MM). Here we explored the role of ADAR1 in the context of MM progression, by focusing on a group of 23 patients in the MMRF CoMMpass Study for which RNAseq and WES datasets exist for matched pre-and post-relapse samples. Our analysis reveals an acquisition of new DNA mutations on disease progression at specific loci surrounding the sites of ADAR associated (A-to-I) RNA editing. These analyses suggest that the RNA editing enzyme ADAR1 can function as a DNA mutator during Multiple Myeloma (MM) progression, and further imply that guide-targeted RNA editing has the capacity to generate specific mutational signatures at predetermined locations. This dual role of RNA editor and DNA mutator might be shared by other deaminases, such as APOBECs, so that DNA mutation might be the result of collateral damage on the genome by an editing enzyme whose primary job is to re-code the cognate transcript toward specific functional outcomes.

Among pollutants, nanoparticles (NPs) consist a potential environmental hazard, as they could possibly harm the aquatic and terrestrial ecosystems while having unpredictable repercussions on human health. Since monitoring the impact of NPs on aquatic and terrestrial life is challenging, due to the differential sensitivities of organisms to a given nanomaterial, the present study examines magnetite nanoparticles' mediated toxicity in different animal models, representing distinctive environments (terrestrial and aquatic). Oxidative, proteolytic and genotoxic effects were evaluated on the hemocytes of the snail Cornu aspersum; in addition to those, apoptotic effects were measured in gills and liver of the zebrafish Danio rerio, and the prussian carp Carassius gibelio. All biochemical parameters studied increased significantly in animals after 8 days exposure to NPs. Inter-species and inter-tissues differences in responses were evident. Our results suggest a common toxicity response mechanism functioning in the tissues of the three animals studied that is triggered by magnetite NPs. The simultaneous use of these parameters could be established after further investigation as a reliable multi-parameter approach for biomonitoring of terrestrial and aquatic ecosystems against magnetite nanoparticles. Additionally, the results of our study could contribute to the design of studies for the production and rational utilization of nanoparticles.