Nucleic acid-based therapeutics have gained increased attention during recent decades because of their wide range of application prospects. Immunostimulatory nucleic acids represent a promising class of potential drugs for the treatment of tumoral and viral diseases due to their low toxicity and stimulation of the body’s own innate immunity by acting on the natural mechanisms of its activation. The repertoire of nucleic acids that directly interact with the components of the immune system is expanding with the improvement of both analytical methods and methods for the synthesis of nucleic acids and their derivatives. Despite the obvious progress in this area, the problem of delivering therapeutic acids to target cells as well as the unresolved issue of achieving a specific therapeutic effect based on activating the mechanism of interferon and anti-inflammatory cytokine synthesis. Minimizing the undesirable effects of excessive secretion of inflammatory cytokines remains an unsolved task. This review examines recent data on the types of immunostimulatory nucleic acids, the receptors interacting with them, and the mechanisms of immunity activation under the action of these molecules. Finally, data on immunostimulatory nucleic acids in ongoing and completed clinical trials will be summarized.
Polyploid species represent a challenge for both cytogenetic and genomic studies due to their high chromosome numbers and the morphological similarity between their paralogous chromosomes. This paper describes the use of low-coverage high-throughput sequencing to identify the 14 most abundant tandemly arranged repetitive elements in the paleotetraploid genome of the crucian carp (Carassius carassius, 2n = 100). These repetitive elements were then used for molecular cytogenetic studies of a closely related functionally triploid form of the Prussian carp (Carassius gibelio, 3n = 150 + Bs) and a relatively distant diploid species, the tench (Tinca tinca, 2n = 48). According to their distribution on the chromosomes of the 3 aforementioned species, the repetitive elements here identified can be divided into 5 groups: (1) those specific to a single genomic locus in both Carassius species, despite the recent carp-specific genome duplication; (2) those located in a single genomic locus of T. tinca, but amplified in one or both Carassius species; (3) those massively amplified in the B chromosomes of C. gibelio; (4) those located in a single locus in C. gibelio, but amplified in many blocks in C. carassius; and (5) those located in multiple pericentromeric loci in both Carassius species. Our data indicate that some of the repetitive elements are highly conserved in cyprinoid species and may serve as good cytogenetic and genomic markers for discriminating paralogous chromosomes, while others are evolutionarily recent, and their amplification may be related to the last whole-genome duplication event.
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