Interferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of infections, they induce expression of antiviral, interferon-stimulated genes (MX1, OAS, IFITM1), and they have immuno-modulatory activities that shape adaptive immune responses. Unlike other IFN, the type III IFN signal through distinct receptors is limited to a few cell types, primarily mucosal epithelial cells. As a consequence of their greater and more durable production in nasal and respiratory tissues, they can determine the outcome of respiratory infections. This review is focused on the role of IFN-λ in the pathogenesis of respiratory viral infections, with influenza as a prime example. The influenza virus is a major public health problem, causing up to half a million lethal infections annually. Moreover, the virus has been the cause of four pandemics over the last century. Although IFN-λ are increasingly being tested in antiviral therapy, they can have a negative influence on epithelial tissue recovery and increase the risk of secondary bacterial infections. Therefore, IFN-λ expression deserves increased scrutiny as a key factor in the host immune response to infection.

Exosomes are natural nanocontainers actively secreted by the body’s cells and transmitting molecular signals of various types to recipient cells. Cellular mechanisms of exosomes’ biogenesis involve specific sorting of RNA for incorporation into them. As a result, the molecular composition of exosomes is closely related to the donor cell’s functional state, and this makes exosomes an important diagnostic and prognostic marker in a number of diseases (primarily oncological). The ability of exosomes to transport biologically active molecules and to protect the cargo from degradation makes them nearly ideal candidates as delivery carriers of RNA in therapeutic or prophylactic regimes. Potential of exosomal surface functionalization enables improved targeting to specific organs, tissues and cells. However, the development of an effective technology for RNA’s loading into exosomes cannot be considered resolved. This review is focused on experimental data on the use of exosomes as vehicles for the delivery of therapeutic and prophylactic RNAs. We briefly consider the biogenesis and functions of exosomes, focusing on those biological properties that make them formidable candidates in the race to develop effective delivery carriers. Furthermore, we describe various techniques of cargo loading into exosomes. Prospects of exosomes application as therapeutic delivery system for siRNAs, miRNAs, and long RNAs are considered.

Development of safe container materials for targeted and controlled drug delivery to the right site in the body is one of the most important aspects of modern biotechnologies. In the last decade, a...

The implementation of RNAi technology into the clinical practice has been significantly postponing due to the issues regarding to the delivery of naked siRNA predominantly to target cells. Here we report the approach to enhance the efficiency of siRNA delivery by encapsulating the siRNA into new carrier systems which are obtained via the combination of widely used layer-by-layer technique and in situ modification by sol-gel chemistry. We used three types of siRNAs (NP-717, NP-1155 and NP-1496) in encapsulated form as new therapeutic agents against H1N1 influenza virus infection. By employing the hybrid microcontainers for the siRNA encapsulation we demonstrate the reduction of viral nucleoprotein (NP) level and inhibition of influenza virus production in infected cell lines (MDCK and A549). The obtained hybrid carriers based on assembled biodegradable polyelectrolytes and sol-gel coating possess several advantages such as a high cell uptake efficiency, low toxicity, efficient intracellular delivery of siRNAs and the protection of siRNAs from premature degradation before reaching the target cells. These findings underpin a great potential of versatile microencapsulation technology for the development of anti-viral RNAi delivery systems against influenza virus infection.

Secretion of extracellular vesicles (EVs) is a fundamental property of living cells. EVs are known to transfer biological signals between cells and thus regulate the functional state of recipient cells. Such vesicles mediate the intercellular transport of many biologically active molecules (proteins, nucleic acids, specific lipids) and participate in regulation of key physiological processes. In addition, EVs are involved in the pathogenesis of multiple diseases: infectious, neurodegenerative, and oncological. The current EV classification into microvesicles, apoptotic bodies, and exosomes is based on their size, pathways of cellular biogenesis, and molecular composition. This review is focused on analysis of the role of EVs (mainly exosomes) in the pathogenesis of viral infection. We briefly characterize the biogenesis and molecular composition of various EV types. Then, we consider EV-mediated pro- and anti-viral mechanisms. EV secretion by infected cells can be an important factor of virus spread in target cell populations, or a protective factor limiting viral invasion. The data discussed in this review, on the effect of EV secretion by infected cells on processes in neighboring cells and on immune cells, are of high significance in the search for new therapeutic approaches and for design of new generations of vaccines.