Triple Combinations of AAV9-Vectors Encoding Anti-HIV bNAbs Provide Long-Term In Vivo Expression of Human IgG Effectively Neutralizing Pseudoviruses from HIV-1 Global Panel.

Anti-human immunodeficiency virus (HIV) broadly neutralizing antibodies (bNAbs) offer a promising approach for the treatment of HIV-1. The current paradigm for antibody therapy involves passive antibody transfer, requiring regular delivery of bNAbs in treating chronic diseases such as HIV-1. An alternative strategy is to use AAV-mediated gene transfer to enable in vivo production of desirable anti-HIV-1 antibodies.

Insight into the electronic structure of the centrosymmetric skyrmion magnet GdRuSi.

The discovery of a square magnetic-skyrmion lattice in GdRuSi, with the smallest so far found skyrmion size and without a geometrically frustrated lattice, has attracted significant attention. In this work, we present a comprehensive study of surface and bulk electronic structures of GdRuSi by utilizing momentum-resolved photoemission (ARPES) measurements and first-principles calculations. We show how the electronic structure evolves during the antiferromagnetic transition when a peculiar helical order of 4f magnetic moments within the Gd layers sets in.

Humanized Mouse Model of HIV Infection.

The development of new drugs for the treatment of HIV infection requires testing of their efficacy in a relevant animal model, such as humanized mice, which, unfortunately, are not yet available in Russia. In the present study, we have developed conditions for the humanization of immunodeficient NSG mice with human hematopoietic stem cells. Humanized animals generated during the study showed a high degree of chimerism and harbored repopulation of the entire range of human lymphocytes required for HIV replication in the blood and organs.

Insight into the Temperature-Dependent Canting of 4f Magnetic Moments from 4f Photoemission.

The orientation of the 4f moments offers an additional degree of freedom for engineering the spin-related properties in spintronic nanostructures of lanthanides. Yet, precise monitoring of the direction of magnetic moments remains a challenge. Here, on the example of the antiferromagnets HoRhSi and DyRhSi, we investigate the temperature-dependent canting of the 4f moments near the surface.

Development of MVA-d34 Tetravalent Dengue Vaccine: Design and Immunogenicity.

Dengue fever, an infectious disease that affects more than 100 million people every year, is a global health problem. Vaccination may be the most effective prevention strategy for the disease. However, the development of vaccines against dengue fever is complicated by the high risk of developing an antibody-dependent increase in infection.

Comparative Evaluation of the Activity of Various Lentiviral Vectors Containing Three Anti-HIV Genes.

A promising direction in the treatment of HIV infection is a gene therapy approach based on the insertion of antiviral genes aimed at inhibiting HIV replication into the genome of host cells. We obtained six constructs of lentiviral vectors with different arrangements of three antiviral genes: microRNAs against the CCR5 gene, the gene encoding the C-peptide, and the gene encoding the modified human TRIM5a protein. We found that despite containing the same genes, these vectors were produced at different titers and had different effects on cell viability, transduction efficiency, and expression stability.

Generation of SARS-CoV-2 Mouse Model by Transient Expression of the Human Gene Mediated by Intranasal Administration of AAV-hACE2.

One of the most important steps in the development of drugs and vaccines against a new coronavirus infection is their testing on a relevant animal model. The laboratory mouse, with well-studied immunology, is the preferred mammalian model in experimental medicine. However, mice are not susceptible to infection with SARS-CoV-2 due to the lack of human angiotensin-converting enzyme (hACE2), which is the cell receptor of SARS-CoV-2 and necessary for the entry of the virus into the cell.

[Generation of SARS-CoV-2 Mouse Model by Transient Expression of the Human ACE2 Gene Mediated by Intranasal Administration of AAV-hACE2].

One of the most important steps in the development of drugs and vaccines against a new coronavirus infection is their testing on a relevant animal model. The laboratory mouse, with well-studied immunology, is the preferred mammalian model in experimental medicine. However, mice are not susceptible to infection with SARS-CoV-2 due to the lack of human angiotensin-converting enzyme (hACE2), which is the cell receptor of SARS-CoV-2 and necessary for the entry of the virus into the cell.

Double and Triple Combinations of Broadly Neutralizing Antibodies Provide Efficient Neutralization of All HIV-1 Strains from the Global Panel.

The use of broadly neutralizing antibodies (bNAbs) is a promising approach to HIV-1 treatment. In this work, we evaluate the neutralizing activity of the following HIV-1 bNAbs: VCR07-523, N6, PGDM1400, CAP256-VRC26.25, 10-1074, PGT128, 10E8, and DH511.

Development of Modified Vaccinia Virus Ankara-Based Vaccines: Advantages and Applications.

Modified vaccinia virus Ankara (MVA) is a promising viral vector for vaccine development. MVA is well studied and has been widely used for vaccination against smallpox in Germany. This review describes the history of the origin of the virus and its properties as a vaccine, including a high safety profile.

Estimating the Orientation of 4f Magnetic Moments by Classical Photoemission.

To use efficiently the magnetic functionalities emerging at the surfaces or interfaces of novel lanthanides-based materials, there is a need for complementary methods to probe the atomic-layer resolved magnetic properties. Here, we show that 4f photoelectron spectroscopy is highly sensitive to the collective orientation of 4f magnetic moments and, thus, a powerful tool for characterizing the related properties. To demonstrate this, we present the results of systematic study of a family of layered crystalline 4f-materials, which are crystallized in the body-centered tetragonal ThCrSi structure.

[HIV Restriction Factor APOBEC3G and Prospects for Its Use in Gene Therapy for HIV].

The mechanisms for the protection of the human body from viral or bacterial agents are extremely diverse. In one such mechanism, an important role belongs to the cytidine deaminase APOBEC3 family, which is the factor of congenital immunity and protects the organism from numerous viral agents. One of the proteins of this family, APOBEC3G, is able to protect against Human Immunodeficiency Virus type 1 in the absence of viral protein Vif.

Immunogenic epitope prediction to create a universal influenza vaccine.

Influenza virus is one of the most rapidly evolving human pathogens and causes significant morbidity and mortality worldwide. This feature enables the virus to avoid natural or vaccine-induced immunity. For this reason, there is an intensive search for new approaches to create a universal influenza vaccine.

Development of a Universal Epitope-Based Influenza Vaccine and Evaluation of Its Effectiveness in Mice.

Vaccination is an effective and economically viable means of protection against the influenza virus, but due to rapid viral evolution, modern seasonal vaccines are not effective enough. Next-generation vaccines are designed to provide protection against a wide range of influenza virus strains, including pandemic variants. In our work, we made an epitope-based universal vaccine, rMVA-k1-k2, against the influenza virus based on the modified vaccinia Ankara (MVA) vector and using our own algorithms to select epitopes from conserved fragments of the NP, M1 and HA proteins of influenza A and B.

Comparison of Recombinant MVA Selection Methods Based on F13L, D4R and K1L Genes.

Modified vaccinia Ankara (MVA) is a promising vaccine vector due to its highly attenuated phenotype and good immunogenicity. However, obtaining a new recombinant MVA remains a tedious and laborious procedure involving many rounds of plaque purification. Recombinant MVA generation can be greatly improved and facilitated by different selection techniques.

[The Titer of the Lentiviral Vector Encoding Chimeric TRIM5α-HRH Gene is Reduced Due to Expression of TRIM5α-HRH in Producer Cells and the Negative Effect of Efla Promoter].

The chimeric protein TRIM5α-HRH is a promising antiviral factor for HIV-1 gene therapy. This protein is able to protect cells from HIV-1 by blocking the virus in the cytoplasm. We are developing protocol of HIV-1 gene therapy, which involves the delivery of the TRIM5α-HRH gene into CD4^(+) T-lymphocytes by lentiviral vectors (LVs).

Application of real-time PCR to significantly reduce the time to obtain recombinant MVA virus.

Obtaining a pure recombinant Modified Vaccinia Ankara (MVA) virus is a multistage, time-consuming procedure. We describe a novel single-tube real-time PCR which enables determination of the amount of wild type and recombinant viruses and their ratio in plaques. Use of the real-time PCR significantly reduce the time and efforts needed to obtain purified recombinant MVA.

[Retrovirus Restriction Factor TRIM5α: The Mechanism of Action and Prospects for Use in Gene Therapy of HIV Infection].

It is commonly known that the antiviral activity of the TRIM5α protein, the intracellular retrovirus restriction factor, underlies the resistance of the Old World monkeys to HIV-1. This fact suggests that TRIM5α can potentially be used to cure HIV-1 infection in humans. The present review considers the mechanisms of HIV-1 replication inhibition by the TRIM5a protein and the prospects for using it in gene therapy of HIV infection.

[Protection of Lymphocytes Against HIV using Lentivirus Vector Carrying a Combination of TRIM5α-HRH Genes and microRNA Against CCR5].

Gene therapy is considered a promising approach to treating infections caused by human immunodeficiency virus (HIV). One strategy is to introduce antiviral genes into cells in order to impart resistance to HIV. In this work, the antiviral activity of new anti-HIV lentiviral vector pT has been studied.

Optimization of Polycistronic Anti-CCR5 Artificial microRNA Leads to Improved Accuracy of Its Lentiviral Vector Transfer and More Potent Inhibition of HIV-1 in CD4⁺ T-Cells.

C-C chemokine receptor type 5 (CCR5) is utilized by human immunodeficiency virus (HIV) as a co-receptor for cell entry. Suppression of the CCR5 gene by artificial microRNAs (amiRNAs) could confer cell resistance. In previous work, we created a lentivector that encoded the polycistron of two identical amiRNAs that could effectively suppress CCR5.

[Tale nucleases--new tool for genome editing].

The ability to introduce targeted changes in the genome of living cells or entire organisms enables researchers to meet the challenges of basic life sciences, biotechnology and medicine. Knockdown of target genes in the zygotes gives the opportunity to investigate the functions of these genes in different organisms. Replacement of single nucleotide in the DNA sequence allows to correct mutations in genes and thus to cure hereditary diseases.

[Downregulation of human CCR5 receptor gene expression using artificial microRNAs].

Chemokine receptor CCR5 is essential for human immunodeficiency virus (HIV) entry into the sensitive cells. The CCR5 inactivation is believed to be one of the promising approaches in HIV therapy, including gene therapy. A powerful mechanism that enables to regulate gene expression is RNA interference which could be exploited to knockdown CCR5 gene.

[Safety of retroviral vectors in gene therapy].

Retroviral vectors are widely used in gene therapy and found to be an effective tool for the delivery of genetic constructs into cells. A unique feature of these vectors is the ability to incorporate therapeutic genes into a chromosome that ensures its passage to all progeny cells and enables to cure the diseases requiring genetic correction of dividing cells such as hematopoietic cells or skin cells. Retroviral vectors have been successfully used in gene therapy clinical trials for the treatment of 2 forms of severe combined immunodeficiencies and some other hereditary blood disorders.

[Treatment of HIV-infection by means of gene therapy].

Current methods of HIV treatment can contain a progression of the disease; however they do not lead to a cure. Lifelong antiretroviral therapy is therefore necessary, leading to problems of cost and toxicity of chemical drugs. The recent advances in science have allowed a new approach to the HIV-treatment - gene therapy.

[Progress in gene therapy].

Recent progress in gene therapy, current status of investigations in this area of experimental medicine are reviewed. Much attention is given to gene-therapeutic approaches the efficacy of which is proved in clinical trials.