Antivirotics based on defective interfering particles: emerging concepts and challenges.

Viruses are obligate parasites, that use the host's internal metabolic systems for their own reproduction. This complicates the search for molecular targets to prevent the spread of viral infection without disrupting the vital functions of human cells. Defective interfering particles (DIPs) are natural competitors of viruses for important resources of viral reproduction.

Challenges in Humoral Immune Response to Adeno-Associated Viruses Determination.

Adeno-associated viruses (AAVs) are non-pathogenic, replication-deficient viruses that have gained widespread attention for their application as gene therapy vectors. While these vectors offer high transduction efficiency and long-term gene expression, the host immune response poses a significant challenge to their clinical success. This review focuses on the obstacles to evaluating the humoral response to AAVs.

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.

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.

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.

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.

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.

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.

Avian Influenza in Wild Birds and Poultry: Dissemination Pathways, Monitoring Methods, and Virus Ecology.

Avian influenza is one of the largest known threats to domestic poultry. Influenza outbreaks on poultry farms typically lead to the complete slaughter of the entire domestic bird population, causing severe economic losses worldwide. Moreover, there are highly pathogenic avian influenza (HPAI) strains that are able to infect the swine or human population in addition to their primary avian host and, as such, have the potential of being a global zoonotic and pandemic threat.

Testate amoeba transfer function performance along localised hydrological gradients.

Testate amoeba transfer functions are widely used for reconstruction of palaeo-hydrological regime in peatlands. However, the limitations of this approach have become apparent with increasing attention to validation and assessing sources of uncertainty. This paper investigates effects of peatland type and sampling depth on the performance of a transfer function using an independent test-set from four Sphagnum-dominated sites in European Russia (Penza Region).

Microarray-based detection of CYP1A1, CYP2C9, CYP2C19, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, NAT2, HLA-DQA1, and AB0 allele frequencies in native Russians.

Xenobiotic-metabolizing genes (e.g., Cytochromes P450, GST, NAT2, and NQO1), folate metabolism genes (e.

Diagnostic microarrays in hematologic oncology: applications of high- and low-density arrays.

Microarrays have become important tools for high-throughput analysis of gene expression, chromosome aberrations, and gene mutations in cancer cells. In addition to high-density experimental microarrays, low-density, gel-based biochip technology represents a versatile platform for translation of research into clinical practice. Gel-based microarrays (biochips) consist of nanoliter gel drops on a hydrophobic surface with different immobilized biopolymers (primarily nucleic acids and proteins).

New triphosphate conjugates bearing reporter groups: labeling of DNA fragments for microarray analysis.

A simple and convenient method for incorporation of fluorescent or ligand groups into 3'-termini of DNA fragments is proposed. A set of triphosphoric acid monoesters bearing fluorescent groups or biotin attached to the triphosphate fragment through linkers of different lengths and structures was synthesized. All the compounds were substrates for calf thymus terminal deoxynucleotidyltransferase and were used for incorporation of marker groups into 3'-termini of DNA fragments.

Clinical screening of gene rearrangements in childhood leukemia by using a multiplex polymerase chain reaction-microarray approach.

Purpose: Currently, many forms of leukemia are considered potentially curable, with prognosis and clinical outcome strongly dependent on the underlying molecular pathophysiology. A substantial number of leukemia patients harbor nonrandom karyotypic abnormalities that define subgroups with unique biological and clinical features. For detection of these types of gene rearrangements, a combination of multiplex RT-PCR with hybridization on oligonucleotide gel array was presented previously, which identified five chromosomal translocations with fusion variants.