MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression by inhibiting the translation of target transcripts. The expression profiles of miRNAs vary in different tissues and change with the development of diseases, including cancer. This feature has begun to be used for the modification of oncolytic viruses (OVs) in order to increase their selectivity and efficacy. OVs represent a relatively new class of anticancer drugs; they are designed to replicate in cancer tumors and destroy them. These can be natural viruses that can replicate within cancer tumor cells, or recombinant viruses created in laboratories. There are some concerns regarding OVs’ toxicity, due to their ability to partially replicate in healthy tissues. In addition, lytic and immunological responses upon OV therapy are not always sufficient, so various OV editing methods are used. This review discusses the latest results of preclinical and clinical studies of OVs, modifications of which are associated with the miRNA-mediated mechanism of gene silencing.

Background: Immune aging is a complex process involving various cellular changes, such as a myeloid bias, decreased functional activity of immune cells, accumulation of senescent cells, and alterations in serum levels of bactericidal humoral factors. As believed, these changes contribute to increased susceptibility of older adults to infectious diseases. Myeloid cells are considered the first line of defense against bacterial invasion. However, it remains unclear whether the protective functions of myeloid cells diminish in active older adults and whether potential age-related changes are evolutionarily conserved across primates. Methods: In this study, myeloid cell populations from peripheral blood and bone marrow of cynomolgus macaques and human peripheral blood were analyzed across a broad age range for phenotypic and functional characteristics, e.g., E. coli phagocytosis, secretion of proinflammatory factors, genetic instability, and signs of cellular aging. Results: Despite minor interspecies phenotypic differences in granulocyte populations, both the quantity and functions of myeloid cells were remarkably stable during aging in both species. Myeloid cells maintained genetic stability, and high SA-β-Gal activity was observed, likely reflecting metabolic traits rather than age-related changes. Importantly, a predominant and age-independent role of humoral factors, rather than cellular mechanisms, was identified in the initial control of bacterial infection. Conclusions: These findings suggest that innate immune functions remain stable for a long time during aging in both species.

Intein-mediated trans-splicing is a powerful tool in modern biotechnology that could be improved through study and optimization of splicing reaction. In this study, we investigated non-standard interactions between three highly homologous pairs of inteins from α-subunit of alpha DNA polymerase III (abbreviated as DnaE) group. This feature is known as cross-reactivity, which could modulate trans-splicing efficiency. Additionally, we combined cross-reactivity with rationally designed mutations in the C part of intein from Synechocystis strain PCC6803 (abbreviated as Ssp DnaE). Combination we found has changed trans splicing efficiency resulting in 1.6-fold increase in GFP fluorescence intensity compared to the original pair. These data could serve as an optimization strategy to develop a more effective protein splicing system that could be applied to non-chromatographic protein purification, antibody and protein complexes engineering, biosensor applications and gene therapy for delivery of large proteins and prime editor complexes that exceed the packaging capacity of viral vectors.

The efficiency of phagocytic activity is a significant organism indicator which decreases with the aging of the immune system. Medications are able to influence phagocytosis, having a blocking or activating effect, and therefore are important modulators of immune function. We are developing an ex vivo assay indispensable for medication screening in human and Macaca fascicularis whole blood. For assay verification, several published control drugs were successfully used. This assay assists with finding medications for enhancing the immune response in elderly people and providing a deeper comprehension of the fundamental process of immune system aging.