Synthetic Promoters in Gene Therapy: Design Approaches, Features and Applications.

Gene therapy is a promising approach to the treatment of various inherited diseases, but its development is complicated by a number of limitations of the natural promoters used. The currently used strong ubiquitous natural promoters do not allow for the specificity of expression, while natural tissue-specific promoters have lowactivity. These limitations of natural promoters can be addressed by creating new synthetic promoters that achieve high levels of tissue-specific target gene expression.

Phylogenetic Insights into H7Nx Influenza Viruses: Uncovering Reassortment Patterns and Geographic Variability.

Influenza A viruses (IAVs), which belong to the Orthomyxoviridae family, are RNA viruses characterized by a segmented genome that allows them to evolve and adapt rapidly. These viruses are mainly transmitted by wild waterfowl. In this study, we investigated the evolutionary processes of H7Nx (H7N1, H7N2, H7N3, H7N4, H7N5, H7N6, H7N7, H7N8, H7N9) viruses, which pose a significant pandemic risk due to the known cases of human infection and their potential for rapid genetic evolution and reassortment.

Molecular Basis of Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine tumors (NETs) are rare well-differentiated neoplasms with limited therapeutic options and unknown cells of origin. The current classification of pancreatic neuroendocrine tumors is based on proliferative grading, and guides therapeutic strategies, however, tumors within grades exhibit profound heterogeneity in clinical manifestation and outcome. Manifold studies have highlighted intra-patient differences in tumors at the genetic and transcriptomic levels.

A Comparative Analysis of Models for AAV-Mediated Gene Therapy for Inherited Retinal Diseases.

Inherited retinal diseases (IRDs) represent a diverse group of genetic disorders leading to progressive degeneration of the retina due to mutations in over 280 genes. This review focuses on the various methodologies for the preclinical characterization and evaluation of adeno-associated virus (AAV)-mediated gene therapy as a potential treatment option for IRDs, particularly focusing on gene therapies targeting mutations, such as those in the and genes. AAV vectors, such as AAV2 and AAV5, have been utilized to deliver therapeutic genes, showing promise in preserving vision and enhancing photoreceptor function in animal models.

Alternative Ways to Obtain Human Mesenchymal Stem Cells from Embryonic Stem Cells.

Differentiation approaches to obtain mesenchymal stem cells (MSCs) have gradually developed over the last few decades. The problem is that different protocols give different MSC types, making further research difficult. Here, we tried three different approaches to differentiate embryonic stem cells (ESCs) from early mesoderm to MSCs using serum-containing or xeno-free differentiation medium and observed differences in the cells' morphology, doubling rate, ability to form colonies, surface marker analysis, and multilineage differentiation potential of the obtained cell lines.

Complex Evolutionary Dynamics of H5N8 Influenza A Viruses Revealed by Comprehensive Reassortment Analysis.

Influenza A viruses (IAVs) circulate among different species and have the potential to cause significant pandemics in humans. This study focuses on reassortment events in the H5N8 subtype of IAV, which poses a serious threat to public health due to its high pathogenicity in birds and potential for cross-species transmission. We retrieved 2359 H5N8 IAV sequences from GISAID, and filtered and analyzed 442 complete genomic sequences for reassortment events using pairwise distance deviation matrices (PDDMs) and pairwise distance correspondence plots (PDCPs).

Establishment of a human induced pluripotent stem cell line (ABi004-A) carrying a compound heterozygous mutation in the KCNV2 gene.

Pathogenic variants in the KCNV2 gene can cause a rare retinal dystrophy that can be inherited recessively, known as cone dystrophy with supernormal rod response (CDSRR). CDSRR leads to specific changes in photoreceptors' electroretinogram response, especially in the rods, poor visual acuity, photophobia, and even maculopathy. The derived iPSC lines from patients with CDSRR may pave the way for apprehension of the pathogenetic mechanism and drug development using in vitro models.

IAVCP (Influenza A Virus Consensus and Phylogeny): Automatic Identification of the Genomic Sequence of the Influenza A Virus from High-Throughput Sequencing Data.

Recently, high-throughput sequencing of influenza A viruses has become a routine test. It should be noted that the extremely high diversity of the influenza A virus complicates the task of determining the sequences of all eight genome segments. For a fast and accurate analysis, it is necessary to select the most suitable reference for each segment.

Abundant Intra-Subtype Reassortment Revealed in H13N8 Influenza Viruses.

Influenza A viruses (IAVs) pose a serious threat to global health. On the one hand, these viruses cause seasonal flu outbreaks in humans. On the other hand, they are a zoonotic infection that has the potential to cause a pandemic.

Codon-optimization in gene therapy: promises, prospects and challenges.

Codon optimization has evolved to enhance protein expression efficiency by exploiting the genetic code's redundancy, allowing for multiple codon options for a single amino acid. Initially observed in , optimal codon usage correlates with high gene expression, which has propelled applications expanding from basic research to biopharmaceuticals and vaccine development. The method is especially valuable for adjusting immune responses in gene therapies and has the potenial to create tissue-specific therapies.

Generation of induced pluripotent stem cell line (MIPTi002-A) derived from a patient with a heterozygous type mutation in the CDC73 gene.

CDC73-related disorders are inherited in an autosomal dominant manner. An individual with a CDC73-related disorder may have inherited the disorder from an affected parent or developed it as the result of a de novo pathogenic variant of CDC73. The iPSC line was obtained by reprogramming the PBMCs of a patient with a heterozygous type mutation of the CDC73 gene.

Generation of induced pluripotent stem line (MIPTi001-A) derived from patient with X-linked adrenoleukodystrophy (X-ALD).

X-linked adrenoleukodystrophy is a metabolic disease associated with mutations in the ABCD1 gene (ATP-binding cassette subfamily D). Numerous pathogenic variants in this gene lead to a wide spectrum of symptoms, including adrenal insufficiency, slowly progressive dying-back axonopathy and demyelination of the central nervous system in specific phenotypes. The induced pluripotent stem cell line was derived from a patient diagnosed with x-ALD.

Gene Therapy Approaches for the Treatment of Hemophilia B.

In contrast to the standard enzyme-replacement therapy, administered from once per 7-14 days to 2-3 times a week in patients with severe hemophilia B, as a result of a single injection, gene therapy can restore F9 gene expression and maintain it for a prolonged time. In clinical research, the approach of delivering a functional copy of a gene using adeno-associated viral (AAV) vectors is widely used. The scientific community is actively researching possible modifications to improve delivery efficiency and expression.

Generation of two human induced pluripotent stem cell lines (ABi001-A and ABi002-A) from cone dystrophy with supernormal rod response patients caused by KCNV2 mutation.

Cone dystrophy with supernormal rod response (CDSRR) is associated with pathogenic variants of the KCNV2 gene that result in severe symptoms, including color vision defects, decreased visual acuity, and specific changes in electroretinogram responses. Two iPSC lines were obtained from two patients in the same family with different types of mutations in the KCNV2 gene. These lines could serve as a useful model for studying the pathogenetic mechanism and treatment development for CDSRR.

AAV genome modification for efficient AAV production.

The adeno-associated virus (AAV) is one of the most potent vectors in gene therapy. The experimental profile of this vector shows its efficiency and accepted safety, which explains its increased usage by scientists for the research and treatment of a wide range of diseases. These studies require using functional, pure, and high titers of vector particles.

Models of Congenital Adrenal Hyperplasia for Gene Therapies Testing.

The adrenal glands are important endocrine organs that play a major role in the stress response. Some adrenal glands abnormalities are treated with hormone replacement therapy, which does not address physiological requirements. Modern technologies make it possible to develop gene therapy drugs that can completely cure diseases caused by mutations in specific genes.

Cap-Independent Circular mRNA Translation Efficiency.

Recently, the mRNA platform has become the method of choice in vaccine development to find new ways to fight infectious diseases. However, this approach has shortcomings, namely that mRNA vaccines require special storage conditions, which makes them less accessible. This instability is due to the fact that the five-prime and three-prime ends of the mRNA are a substrate for the ubiquitous exoribonucleases.

Characterizing and Quenching Autofluorescence in Fixed Mouse Adrenal Cortex Tissue.

Tissue autofluorescence of fixed tissue sections is a major concern of fluorescence microscopy. The adrenal cortex emits intense intrinsic fluorescence that interferes with signals from fluorescent labels, resulting in poor-quality images and complicating data analysis. We used confocal scanning laser microscopy imaging and lambda scanning to characterize the mouse adrenal cortex autofluorescence.

Robust AAV Genotyping Based on Genetic Distances in Rep Gene That Are Maintained by Ubiquitous Recombination.

Adeno-associated viruses (AAVs) are a convenient tool for gene therapy delivery. According to the current classification, they are divided into the species AAV A and AAV B within the genus Dependoparvovirus. Historically AAVs were also subdivided on the intraspecies level into 13 serotypes, which differ in tissue tropism and targeted gene delivery capacity.

Universal Flu mRNA Vaccine: Promises, Prospects, and Problems.

The seasonal flu vaccine is, essentially, the only known way to prevent influenza epidemics. However, this approach has limited efficacy due to the high diversity of influenza viruses. Several techniques could potentially overcome this obstacle.

Boosting of the SARS-CoV-2-Specific Immune Response after Vaccination with Single-Dose Sputnik Light Vaccine.

Despite measures taken world-wide, the coronavirus disease 2019 (COVID-19) pandemic continues. Because efficient antiviral drugs are not yet widely available, vaccination is the best option to control the infection rate. Although this option is obvious in the case of COVID-19-naive individuals, it is still unclear when individuals who have recovered from a previous SARS-CoV-2 infection should be vaccinated and whether the vaccination raises immune responses against the coronavirus and its novel variants.