edicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases and gene therapy (A61K48)

Single-chemical nucleic acid molecules for gene expression control // 2628311
FIELD: biotechnology.SUBSTANCE: invention relates to biochemistry, in particular to a single-stranded nucleic acid molecule that inhibits target gene expression. The said molecule in the order from the 5'-end to the 3'-end contains the 5'-end portion Xc, the linker portion Lx, the inner portion Z, the linker portion Ly and the 3'-end portion Yc. At that, the inner region Z consists of the inner 5'-end portion X that is complementary to the 5'-end portion Xc and the inner 3'-end portion Y that is complementary to the 3'-end portion Yc. At that, Z consists of 19-30 bases and contains a sequence that suppresses the target gene expression. Z-(Xc+Yc) from 0 to 4 bases, Xc from 1 to 11 bases and Yc from 1 to 11 bases. This invention also discloses a method, application and composition for target gene expression inhibition, method, use and pharmaceutical composition for treatment of a disease caused by an increase in target gene expression using the above-mentioned nucleic acid molecule and the use of such molecule to induce RNA interference.EFFECT: invention allows application of a single-stranded nucleic acid molecule for patients treatment, since it does not cause a side effect in the form of interferon induction.32 cl, 32 dwg, 7 tbl, 25 ex
ethods for pathological changes detection in organ or system of organs // 2626540
FIELD: biotechnology.SUBSTANCE: methods for pathology detection in an organ or organ system, a method for identification of a compound suitable for slowing the progression or treatment of a pathology of an organ system, and a method for determination of compound or environmental factor toxicity for a system of organs. Methods for pathology detection in organs or organ systems include measurement of microRNA, with which an organ or an organ system is enriched, measurement of normalizing microRNA level in the same sample of biological fluid, microRNA levels ratio calculation and microRNA levels ratio comparison with the appropriate control ratio. At that, in the method for compound identification, measurement of the microRNA level and the normalizing microRNA level is performed before and after administration of the test compound for comparison. In the method for compound or environmental factor toxicity determination, microRNA is measured and the level of the normalizing microRNA is measured also before and after exposure to the said compound or factor to compare them.EFFECT: inventions provide early detection of pathological changes in an organ system or in a particular organ of the individual.58 cl, 148 dwg, 11 tbl, 8 ex

ethods and formulations for cells transfection // 2624139
FIELD: biotechnology.SUBSTANCE: method for cell reprogramming for a less differentiated state is described, comprising culturing of a differentiated cell in a reprogramming medium containing albumin, wherein albumin is treated by ion exchange resin or charcoal, transfecting of a cell of one or more synthetic RNA molecules, wherein the said one or more synthetic RNA molecules include at least one RNA molecule encoding one or more reprogramming factors, and wherein the transfection yields cells expressing one or more reprogramming factors; and repeating of step (b) at least twice for 5 consecutive days to obtain cells reprogrammed for a less differentiated state. A medium for cells culturing for reprogramming for a less differentiated state is described, comprising: Dulbecco modified Eagle's medium: F-12 medium (DMEM/F12), 10 mcg/ml of insulin, 5.5 mcg/ml of transferrin, 6.7 ng/ml of sodium selenite, 20 ng/ml of basic fibroblast growth factor (bFGF) and 5 mg/ml of albumin, wherein albumin is treated by ion exchange resin and/or charcoal. Also a medium for cells culturing for reprogramming for a less differentiated state is described, comprising: Dulbecco modified Eagle's medium: F-12 medium (DMEM/F12), 10 mcg/ml of insulin, 5.5 mcg/ml of transferrin, 6.7 ng/ml of sodium selenite, 20 ng/ml of basic fibroblast growth factor (bFGF) and 5 mg/ml of albumin, wherein less than 0.65% of albumin dry weight include lipids and/or less than 0.35% of albumin dry weight comprises free fatty acids.EFFECT: invention expands the arsenal of ways to transfer cells to a less differentiated state.28 cl, 11 dwg, 2 tbl, 29 ex

Treatment of diseases associated with the sialidase 4 (neu4) gene, by gene neu4 natural antisense transcript inhibition // 2624048
FIELD: biotechnology.SUBSTANCE: methods for sialidase gene 4 (NEU4) expression increase using an oligonucleotide that specifically binds to gene NEU4 natural antisense polynucleotide. An oligonucleotide with length from 10 to 30 nc is presented, which specifically binds to a natural antisense polynucleotide for NEU4 gene. A pharmaceutical composition comprising an effective amount of the said oligonucleotide is presented as well.EFFECT: group of inventions allows to increase NEU4 gene expression which is useful for treatment or prevention of diseases associated with NEU4 gene or a product encoded by the gene.36 cl, 1 dwg, 1 tbl, 2 ex

ethods and compositions for modeling expression of apolipoprotein (a) // 2624028
FIELD: biotechnology.SUBSTANCE: obtained modified antisense compounds are able to specifically inhibit the expression of the nucleic acid apo (a). The invention may be used as a medicament for treating, preventing or slowing the progression of disease associated with increased apo (a) or Lp (a), at an individual in need thereof.EFFECT: reduced expression of apolipoprotein mRNA and protein in an animal, and can be used in medicine.23 cl, 65 tbl, 13 ex
ethod to obtain optimized solid gene-activated material, method to obtain solid carrier matrix, optimized solid gene-activated material for tissue regeneration // 2623171
FIELD: biotechnology.SUBSTANCE: method for production of an optimized solid gene-activated material is described, comprising creation of a carrier matrix that binds at least one nucleic acid molecule, followed by placing at least one additional nucleic acid molecule on its surface by any physical method allowing such placement without chemical bond formation between the said carrier matrix and the additional nucleic acid. Also a process for preparation of a solid carrier matrix used in the method described and intended for binding of at least one nucleic acid molecule, comprising introduction of any complexing agent into the solid matrix carrier at the stage of its synthesis by treating the initial material with a solution containing a metal-complexing agent salt capable of binding of at least one nucleic acid molecule is provided. Products obtained by these methods are presented as well.EFFECT: invention allows to receive optimized osteoplastic materials having an accurate dose of nucleic acids, more efficient dynamics of gene structures release from carrier matrix structure and increased level of recipient bed cells transfection by the biologically active substance.5 cl, 5 dwg, 2 tbl, 2 ex

Treatment of diseases associated with erythropoietin (epo) by natural epo antisense transcript inhibition // 2620970
FIELD: medicine.SUBSTANCE: invention relates to biotechnology. A synthetic optionally modified oligonucleotide is described, with length of 10-30 nucleotides or 19-30 nucleotides, wherein the modification is selected from a modified sugar fragment; modified internucleotide bond; modified nucleotide, and combinations thereof. At that, the said oligonucleotide is an antisense compound that hybridizes with natural antisense polynucleotide having SEQ ID NO:3, and causes stimulation of erythropoietin gene expression. A method is also disclosed for stimulation of erythropoietin polynucleotide expression, having the sequence SEQ ID NO:1 or 2 in patient's cells or tissues, comprising application of the described oligonucleotide. A method is also disclosed for stimulation of erythropoietin gene expression in mammalian tissues or cells in vivo or in vitro, comprising bringing the said cells or tissues in contact with at least one siPHK oligonucleotide, 19-30 nucleotides in length, wherein at least one said siPHK oligonucleotide is specific against the natural antisense erythropoietin polynucleotide selected from SEQ ID NO: 3. A composition is provided for stimulation of erythropoietin gene expression in cells or tissues of a mammal comprising one or more oligonucleotide described and a pharmaceutically acceptable excipient.EFFECT: invention expands the arsenal of treatment of diseases associated with erythropoietin.25 cl, 6 dwg, 5 ex

Treatment of hbv infection // 2620966
FIELD: pharmacology.SUBSTANCE: invention relate to the means for directed DNA of RNA interference (ddRNAi) (versions) for inhibiting the expressions of RNA-dependent DNA polymerase of hepatitis B virus (HBV), an expression cassette for expressing the means for ddRNAi, an expression vector for ddRNAi, a pharmaceutical composition comprising means for ddRNAi and their use for treatment of the infections caused by hepatitis B, of individuals. The characterized means comprises, in the direction from 5' to 3': the first effector sequence with a length of 18-22 nucleotide, the first effector complementary sequence, the second effector sequence with a length of 18-22 nucleotides, and the second effector complementary sequence; the third effector sequence with a length of 18-22 nucleotides; and the third effector complementary sequence, where each effector sequence is, substantially, complementary to the section of the predicted gene transcript of RNA-dependent DNA polymerase. Several effectors may target the same HBV gene section, different (possibly overlapping) sections of the same gene, and/or different HBV genes.EFFECT: possibility of using the invention for targeting the HBV expression in the cells for the treatment of HBV infection.16 cl, 10 dwg, 6 tbl, 9 ex
aterials and method for modulation of proliferation and differentiation of regulatory, stem and other somatic cells // 2620069
FIELD: biotechnology.SUBSTANCE: invention can be used for treatment and prevention of diseases, disorders or conditions associated with impaired cell proliferation and differentiation processes in various organs and tissues, for activation of the regeneration capacity of human and animal organs and tissues in case of age-related changes and after extreme impacts, as well as for biomedical research. This invention can be widely used in blood transfusion, organ transplantation, as well as serve as a general approach to development of reliable ways to treat age-related changes in the elderly. The invention can be also used in cosmetic industry for production of active ingredients to enhance regeneration and improve head, face and body skin, in particular, to manufacture active ingredients for anti-aging treatment to eliminate skin defects, for stimulation and acceleration of hair growth, for combating with hirsutism.EFFECT: increased efficiency of application.50 cl, 3 dwg, 25 tbl, 13 ex

Treatment of diseases associated with uncoupling proteins 2 (ucp2), by inhibiting of natural antisense transcript to ucp2 // 2619185
FIELD: medicine, pharmacy.SUBSTANCE: invention refers to biochemistry. Oligonucleotides with length of 15 - 30 nucleotides are described, that specifically hybridize to natural antisense IRS2 sequence and have a sequence similar to the one inversely complementary with the portion of SEQ ID NO: 3 sequence by at least 80%, have a sequence similar to the portion of SEQ ID NO: 1 sequence by at least 80%, wherein the said oligonucleotides optionally contain one or more modifications selected from the following: at least one modified sugar unit, at least one modified internucleoside linkage, at least one modified nucleotide and combinations thereof; and their application for treatment of diseases and disorders associated with the expression of UCP2.EFFECT: invention expands the arsenal of tools for treatment of diseases and disorders associated with the expression of UCP2.28 cl, 1 dwg, 2 ex

Antisense nucleic acids // 2619184
FIELD: biotechnology.SUBSTANCE: antisense oligomer is described which causes 50th exon skipping in the human dystrophin gene consisting of a nucleotide sequence complementary to any of the nucleotide sequences consisting of the 106 th - 126 th, 107 th - 127 th, 108 th - 127 th, 108 th - 128 th or 109 th - 129 th nucleotides, counting from the 5-terminus of the 50th' exon of human dystrophin gene. A pharmaceutical composition for muscular dystrophy treatment is also described, which comprises an antisense oligomer or a pharmaceutically acceptable salt or hydrate thereof, as an active ingredient.EFFECT: invention expands the range of agents for muscular dystrophy treatment.12 cl, 31 dwg, 15 tbl, 54 ex

Lentiviral vectors pseudotyped by mutant baev glycoproteins // 2618864
FIELD: biotechnology.SUBSTANCE: pseudotyped viral vector particle for biological material transfer into hematopoietic cells, a method for its preparation and application, a drug for hematopoietic disorders or autoimmune diseases treatment, comprising said particles, a method for hematopoietic cells transducing and a stable virus packing cell line are proposed. The proposed pseudotyped viral vector particle is lentiviral and contains a chimeric enveloped glycoprotein or a modified envelope glycoprotein of baboon endogenous retrovirus (BaEV). This chimeric enveloped glycoprotein contains a transmembrane domain and an extracellular envelope BaEV glycoprotein and cytoplasmic tail domain of the enveloped glycoprotein of the murine leukemia virus (MLV). The modified enveloped BaEV glycoprotein does not contain the fusion inhibiting R peptide in the cytoplasmic tail domain.EFFECT: proposed vector particle efficiently transduces hematopoietic cells and can be used in genetic therapy.13 cl, 27 dwg, 2 tbl, 1 ex

Treating diseases associated with nuclear respiratory factor 1 (nrf1) by inhibition of natural antisense transcript to nrf1 // 2615450
FIELD: biochemistry.SUBSTANCE: invention relates to biochemistry. Invention describes antisense oligonucleotides, modulating expression of nuclear respiratory factor 1 (NRF1), in particular by targeted interaction with natural antisense polynucleotides of nuclear respiratory factor 1 (NRF1). Wherein antisense oligonucleotide is oligonucleotide with length from 19 to 30 nucleotides, which is specifically hybridized with natural antisense polynucleotide of NRF1 and has sequence, at least 90 % identical to sequence, back complementary to section within 1 to 810 nucleotide of sequence SEQ ID NO: 2, or has the sequence, at least at 90 % identical to the section of the sequence SEQ ID NO: 1, wherein said oligonucleotide optionally contains one or more modifications, selected from: at least one modified sugar fragment; at least one modified internucleotide linkage; at least one modified nucleotide; and their combinations. Invention also relates to their application for treating diseases and disorders associated with expression of NRF1.EFFECT: invention enables increasing gene expression of nuclear respiratory factor 1.30 cl, 1 dwg, 2 ex

edicinal agent for treating hepatic fibrosis, method for production thereof and method of treating hepatic fibrosis // 2615445
FIELD: biochemistry.SUBSTANCE: invention relates to biochemistry, biotechnology and genetic engineering, in particular, to a drug for treating hepatic fibrosis based on a mixture of two non-viral plasmid structures. First non-viral plasmid structure is pC4W-HGFopt and comprises a gene, which codes human hepatocyte growth factor. Second is a pVax1-UPAopt and contains a gene coding human urokinase. In said drug plasmid structures are contained in following concentrations: pC4W-HGFopt – from 0.5 to 0.7 mg/ml; pVax1-UPAopt – from 0.3 to 0.5 mg/ml, wherein total concentration of DNA is 1±0.01 mg/ml. Present invention discloses a method of producing said drug and method of treating hepatic fibrosis using said drug in a pharmaceutically acceptable amount.EFFECT: present invention enables to produce a drug for treating hepatic fibrosis, having higher efficiency, which is safe and easy to produce.12 cl, 28 dwg, 4 tbl, 9 ex

ethod for reparative angiogenesis stimulation and connective tissue regeneration in case of its damage, by the genetic therapy method using species-specific vegf and fgf2 protein factors genes in veterinary medicine, and genetic structure for implementation of method // 2614665
FIELD: medicine.SUBSTANCE: method for reparative angiogenesis stimulation and connective tissue regeneration in case of its damage and/or disease by introduction of a genetic engineering DNA construct where genes encoding the expression of species-specific horse VEGF164 and FGF2 protein factors are cloned, into a horse body. Genetic construct DNA SEQ ID NO: 1 is proposed for implementation of the aforementioned method.EFFECT: efficient means and methods for reparative angiogenesis and connective tissue regeneration stimulation.6 cl, 8 dwg, 2 ex

Immunity-inducing means // 2614386
FIELD: biotechnology.SUBSTANCE: invention refers to production of means containing at least one polypeptide selected from SEQ ID NO: 4, 2, 8, 10 and 12, and/or recombinant vector(s), comprising polynucleotide(s) encoding at least one polypeptide, as the active ingredient(s), and can be used in medicine. The resulting means is used for efficient induction of T-cell immunity against malignancies expressing KATNAL1.EFFECT: invention allows to obtain antigen-presenting cells presenting the polypeptide obtained from KATNAL1, and to effectively induce cytotoxic cells against KATNAL1, which is efficient as a therapeutic agent against malignant neoplasms expressing KATNAL1.7 cl, 3 dwg, 3 ex

Reduction of level of lactate and increasing of production of polypeptide by inhibiting expression of lactate dehydrogenase and pyruvate dehydrogenase kinase // 2614125
FIELD: biotechnology.SUBSTANCE: invention relates to biotechnology and concerns method of reducing lactate production in mammalian cells, method of silencing or reduction in mammal cell of transcription of lactate dehydrogenase (LDH) and pyruvate dehydrogenase kinase (PDHK), method of producing mammal cells, which exhibits low production of lactate in culture, vector containing first heterologous nucleotide sequence coding small interfering RNA (siRNA), specific for lactate dehydrogenase, and second heterologous nucleotide sequence coding siRNA specific for pyruvate dehydrogenase kinase, each of which is connected with its promoter.EFFECT: presented inventions allow reducing in cultured cells production of lactate and increasing of production of heterologous polypeptide.40 cl, 6 dwg

Treatment of diseases associated with colonystimulating factor 3 (csf3) by inhibition of natural antisense transcript to csf3 // 2612884
FIELD: biochemistry.SUBSTANCE: invention relates to biochemistry. Invention describes modified oligonucleotides with length from 15 to 30 nucleotides, containing at least one modification, wherein said at least one modification is selected from: at least one modified sugar fragment; at least one modified internucleotide linkage; at least one modified nucleotide; and their combinations. Wherein said oligonucleotides are specifically hybridized with natural antisense CSF3 gene polynucleotide and have sequence at least by 80 % identical to sequence, back complementary section within nucleotides from 1 to 742 of SEQ ID NO: 2, or have sequence at least by 80 % identical to section of sequence SEQ ID NO: 1. Invention also relates to use of such antisense oligonucleotides for treating diseases and disorders associated with expression of CSF3.EFFECT: invention extends range of products for treating diseases and disorders associated with expression of CSF3.30 cl, 1 dwg, 1 tbl, 2 ex

Vectors conditionally expressing therapeutic proteins, host cells comprising the vectors, and uses thereof // 2612788
FIELD: medicine.SUBSTANCE: present invention relates to gene therapy for treating eye diseases, more specifically to use vectors for conditional expression of one or more therapeutic protein under the control of gene expression modulation system in the presence of activating ligand in the preparing of a drug, and can be used in medicine.EFFECT: present invention allows to engineer a conditional expression vectors, which can be used for treating macular degeneration or glaucoma in an individual.10 cl, 40 dwg, 8 tbl, 12 ex

Optimized nucleotide sequence and pharmaceutical compositions based thereon with sustained vegf transgene expression // 2612497
FIELD: biotechnology.SUBSTANCE: way to extend the lifetime of vegf transgene mRNA in a mammal cell transfected with the genetic structure. Point deletions of 3'noncoding region of the vascular endothelial growth factor (Vegf) gene are performed, at that, the deleted nucleotide is not replaced or replaced by cytosine in guanine or adenine substitution points. Then, mRNA lifetime is determined for each deletion. Data is analyzed and a genetic structure is designed, comprising 3'noncoding region with aggregated single deletions and/or cytosine substitutions, which showed the best results in terms of mRNA lifetime extension. In addition, versions of plasmid DNA, constructed to implement the said method, and vegf transgene mRNA obtained by plasmid DNA transcription, are proposed. The invention also relates to plasmid DNA aplication, including its use as part of a pharmaceutical composition for tissue regeneration.EFFECT: invention allows to increase overall therapeutic vegf protein production due to an increased mRNA lifetime achieved by introduction of optimal changes in the vegf gene 3'UTR sequence.8 cl, 9 dwg, 2 tbl, 2 ex

Treatment of pancreatic developmental gene related diseases by inhibition of natural antisense transcript to pancreatic developmental gene // 2612161
FIELD: chemistry.SUBSTANCE: present invention relates to antisense oligonucleotides, modulating expression of pancreatic developmental gene, in particular, by targeted interaction with natural antisense polynucleotides of pancreatic developmental gene. Said oligonucleotides have a length from 15 to 30 nucleotides, have a sequence at least 90 % identical to sequence, inverse to complementary section from 1 to 1 235 nucleotide sequence SEQ ID SEQ ID NO: 6, from 1 to 17 964 nucleotide sequence SEQ ID NO: 7, from 1 to 50 003 nucleotide sequence SEQ ID SEQ ID NO: 8, from 1 to 486 nucleotide sequence SEQ ID NO: 9, from 1 to 494 nucleotide sequence SEQ ID NO: 10, from 1 to 1 992 nucleotide sequence SEQ ID NO: 11, or from 1 to 1 767 nucleotide sequence SEQ ID NO: 12, or have a sequence, at least 90 % identical to section of sequence selected from SEQ ID NOS: 1-5, and are specifically hybridised with natural antisense polynucleotide, selected from SEQ ID NOS: 6-12, wherein said oligonucleotides can optionally contain one or more modifications, selected from following: at least one modified sugar fragment, at least one modified inter-nucleoside bond, at least one modified nucleotide and combination thereof. Present invention also relates to use of such antisense oligonucleotides for treating diseases and disorders, associated with expression of pancreatic developmental genes.EFFECT: invention widens range of products for treating diseases and disorders associated with expression of pancreatic developmental genes.31 cl, 5 dwg, 1 tbl, 2 ex

Virions of adeno-associated virus with optional capsid and methods of their use // 2611202
FIELD: medicine; biotechnology.SUBSTANCE: invention relates to biotechnology, virology, and medicine. Virions of adeno-associated virus (AAV) with optional capsid protein are presented, where AAV virions show high infection load of retinal cell at intravitreal injection compared with wild type AAV. Methods of delivering gene product in retinal cell of person and methods of treating eye diseases are also described.EFFECT: virions of adeno-associated virus with optional capsid and methods for using them are presented.24 cl, 25 dwg, 2 tbl, 3 ex

Treatment of rnase h1 related diseases by inhibition of natural antisense transcript to rnase h1 // 2611192
FIELD: biotechnology.SUBSTANCE: oligonucleotides are discribed that enhance RNase H1 gene expression via targeted contact with natural antisense polynucleotides RNase H1.The present invention also relates to the use of the described oligonucleotides for treatment of diseases and disorders associated with RNase H1 expression.EFFECT: creation of additional means for treatment of diseases and disorders associated with RNase H1 expression.30 cl, 1 dwg, 2 ex

Treatment of diseases, associated with sex hormones binding globulin (shbg), by inhibition of natural antisense transcript to shbg // 2611191
FIELD: biochemistry.SUBSTANCE: invention relates to biochemistry. Invention describes antisense oligonucleotides, modulating expression of sex hormones binding globulin (SHBG), in particular by targeted interaction with natural antisense polynucleotides of sex hormones binding globulin (SHBG). Present invention also relates to use of such antisense oligonucleotides for treating diseases and disorders, associated with SHBG expression. Said oligonucleotides have length from 19 to 30 nucleotides, wherein they are specifically hybridized with natural antisense polynucleotide of SHBG gene and have sequence identical at least by 90 % to sequence reverse complementary to section within from 1 to 3016 nucleotide of sequence SEQ ID NO: 2 or within from 1 to 1609 nucleotide of sequence SEQ ID NO: 3, or have sequence, identical at least by 90 % to section of sequence SEQ ID NO: 1, wherein they can optionally contain one or more modifications, selected from following: at least one modified sugar fragment, at least one modified internucleoside link, at least one modified nucleotide and their combinations.EFFECT: invention extends range of products for treating diseases and disorders, associated with SHBG expression.32 cl, 1 dwg, 2 ex

Treatment of diseases related with gene dlg by inhibition of natural antisense transcript of dlg gene // 2611190
FIELD: biochemistry.SUBSTANCE: invention relates to biochemistry. Described an oligonucleotide with length approximately from 15 to 30 nucleotides, containing at least one modification, note here that said at least one modification selected from: at least one modified sugar residue; at least one modified internucleotide linkage; at least one modified nucleotide; and their combinations. Note here that said oligonucleotide is hybridized with natural antisense transcript of gene Discs large homolog 1 (DLG1) and has the sequence, at least at 80 % identical to reverse component of section of the sequence SEQ ID NO: 2, or has the sequence, at least at 80 % identical to the section of the sequence SEQ ID NO: 1. Invention also relates to use of said antisense oligonucleotide for treatment diseases and disorders associated with expression of gene DLG1.EFFECT: invention extends the range of agents for treatment diseases and disorders associated with DLG gene expression.33 cl, 2 dwg, 1 tbl, 3 ex

Treatment diseases, associated with interferon-regulatory factor 8 (irf8), by inhibition of natural antisense transcript to irf8 // 2611187
FIELD: chemistry.SUBSTANCE: present invention relates to antisense oligonucleotides, modulating expression and/or function of interferon-regulatory factor 8 (IRF8), in particular, by targeted interaction with natural antisense polynucleotides of interferon regulatory factor 8 (IRF8).EFFECT: present invention also relates to identification of such antisense oligonucleotides and use thereof in treating diseases and disorders associated with expression of IRF8.32 cl, 1 dwg

Treatment of tumor protein 63 (p63) related diseases by inhibition of natural antisense transcript to p63 // 2611186
FIELD: biochemistry.SUBSTANCE: invention relates to biochemistry. Described oligonucleotides with length from 15 to 30 nucleotides, containing at least one modification, note here that said at least one modification selected from: at least one modified sugar fragment; at least one modified internucleotide linkage; at least one modified nucleotide; and their combinations. Note here that said oligonucleotides are specifically hybridized with natural antisense polynucleotide of gene p63, increasing such way gene expression of tumor protein 63 (p63) in vivo or in vitro, and have sequence at least at 90% identical to sequence, reverse complementary to a section within from 1 to 288 nucleotide sequence SEQ ID NO: 2, or have sequence, at least at 90% identical to a section of sequence SEQ ID NO: 1. Present invention also relates to use of such antisense oligonucleotides for treatment of diseases and disorders associated with expression of p63.EFFECT: invention extends the range of products for treating diseases and disorders associated with expression of p63.33 cl, 1 dwg, 2 ex

Treatment of fibroblast growth factor 21 (fgf21) related diseases by inhibition of natural antisense transcript to fgf21 // 2610661
FIELD: biotechnology.SUBSTANCE: described oligonucleotides, that increase expression of a gene of fibroblast growth factor 21 (FGF21), by interaction with the natural targeting antisense polynucleotides fibroblast growth factor 21 (FGF21). The present invention also relates to the use of the described oligonucleotides for the treatment of diseases and disorders associated with the expression of FGF21.EFFECT: invention expands the arsenal of tools aimed for the treatment of diseases and disorders associated with the expression of FGF21.26 cl, 2 dwg, 3 ex, 1 tbl

Treatment of diseases, associated with hepatocyte growth factor (hgf), by inhibition of natural antisense transcript to hgf // 2609631
FIELD: biochemistry.SUBSTANCE: invention relates to biochemistry. Invention describes oligonucleotides, modulating expression of hepatocyte growth factor (HGF), in particular, by means of targeted interaction with natural antisense polynucleotides of hepatocyte growth factor (HGF). Present invention also relates to the use of mentioned oligonucleotides for treating diseases and disorders, associated with HGF expression.EFFECT: invention extends range of products for treating diseases and disorders, associated with HGF expression.32 cl, 1 dwg, 2 ex

ethods and compositions for treating hemophilia b // 2608643
FIELD: biochemistry.SUBSTANCE: described protein which binds to genome factor IX (FIX), polynucleotide coding such protein, recovered host cell expressing the protein and method for protein expression. Presented protein includes genetically engineered DNA-binding domain of protein of "zinc finger" type, where DNA-binding domain contains four or five regions of recognising"zinc finger".EFFECT: presented inventions can be used in clinical practice in patients with hemophilia B.15 cl, 5 dwg, 1 tbl, 5 ex

Treating diseases, associated with nanog, by inhibition of natural antisense nanog transcript // 2608493
FIELD: biochemistry.SUBSTANCE: invention relates to biochemistry. Methods of increasing NANOG polynucleotide expression with help of oligonucleotides with length from 19 to 30 nucleotides are disclosed. Corresponding oligonucleotides and composition, containing them, are described.EFFECT: method of preventing or treating diseases, associated with at least one NANOG polynucleotide and/or at least one product, coded by said polynucleotide is also described, including: administering to patient of therapeutically effective dose of at least one described oligonucleotide.35 cl, 1 dwg, 1 tbl, 2 ex

Serotonin 5-ht3 receptor antagonists for application in treatment of lesional vestibular disorders // 2608458
FIELD: medicine.SUBSTANCE: invention relates to medicine and consists in application of serotonin 5-HT3 receptor antagonist for treatment of damages during vestibular disorders, wherein, mentioned damage is characterized by damage of internal ear cells and/or vestibular nerve cells, wherein, serotonin 5-HT3 receptor antagonist is selected from a group comprising ondansetron, palonosetron, tropisetron, lerisetron, alosetron, granisetron, dolasetron, bernesetron, ramosetron, azasetron, itasetron, zakoprid and cilansetron; and mentioned serotonin 5-HT3 receptor antagonist is introduced to the patient, at least during 5 days.EFFECT: treatment of damages during vestibular disorders.4 cl, 4 ex, 6 dwg

Novel viral vector construct for neuron specific continuous dopa synthesis in vivo // 2606012
FIELD: medicine.SUBSTANCE: inventions relate to dicistronic expression vector, its application for amelioration of Parkinson's disease, pharmaceutical composition and a method for determining the expression ratio of polypeptide of GTP-cyclohydrolase 1 and polypeptide of tyrosine hydroxylase expressed by said dicistronic vector. Presented vector contains the first top expression cassette along the transcription and the second lower expression cassette along the transcription. Said first top expression cassette along the transcription contains nucleotide sequence containing the first promoter sequence functionally connected with the first nucleotide sequence, wherein said first nucleotide sequence encodes GTP-cyclohydrolase 1 polypeptide (GCH1; EC 3.5.4.16). Said second lower expression cassette along the transcription contains nucleotide sequence containing the second promoter sequence functionally connected with the second nucleotide sequence. Said second nucleotide sequence encodes tyrosine hydroxylase polypeptide (TH; EC 1.14.16.2). At that, the vector is adeno-associated vector (AAV) and said second nucleotide sequence is functionally related to woodchuck posttranscriptional regulatory element (WPRE). Said first and second promoters are promoters of synapsin 1, the first top expression cassette along the transcription and second lower expression cassette along the transcription contain polyadenylation sequence, and expression cassettes of the dicistronic expression vector contain 5'-end repeated sequence and 3'-end repeated sequence. Polypeptides of tyrosine hydroxylase and GTP-cyclohydrolase 1 can be expressed in ratio from 3:1 to 7:1, respectively. Inventions can be used for recovery of catecholamine balance in a subject in need thereof.EFFECT: present invention is applicable for treating disorders associated with dopamine deficiency.21 cl, 8 dwg, 1 tbl, 3 ex

ethod for screening substances having weight control effect // 2603745
FIELD: biotechnology.SUBSTANCE: invention relates to genetic engineering, particularly, to screening of substances having weight control effect, and can be used in medicine. Method of screening substances having weight control effect, involves bringing test substance into contact with cells expressing Synoviolin gene, and identifying whether above test substance has or not inhibiting effect on Synoviolin gene expression. Pharmaceutical compositions include nucleic acid, which suppresses Synoviolin gene expression, or Synoviolin protein ubiquitinylation activity inhibitor.EFFECT: invention makes it possible to effect on weight reduction by inhibition of gene expression or Synoviolin protein activity.4 cl, 5 dwg, 1 ex

Particulate substances comprising ceramic particles for delivery of biomolecules // 2600841
FIELD: medicine.SUBSTANCE: series of inventions relates to medicine. A particulate substance is described that comprising: particles of a ceramic matrix bearing a functional group, which is capable of promoting penetration of the particles into cells; and a biomolecule disposed within pores of the particles, where said biomolecule being releasable from the particles by dissolution of the ceramic matrix.EFFECT: agent provides good penetration of the active substance in target cells.56 cl, 22 dwg

ethod for gene therapy treatment of diabetic foot syndrome // 2599507
FIELD: medicine.SUBSTANCE: present group of inventions relates to medicine. Disclosed is the use of pCMV-VEGF plasmid splicing version 165 (Seq # 1) for treating diabetic foot syndrome and method for treating diabetic foot syndrome.EFFECT: presented group of inventions provides improved treatment results for diabetic foot by means of gene therapy.3 cl, 3 dwg, 4 tbl

Tissue-regeneration promoter using recruitment of bone marrow mesenchymal stem cells and/or pluripotent stem cells in blood // 2599448
FIELD: medicine.SUBSTANCE: presented inventions relate to use of an agent stimulating tissue regeneration, and a method of stimulating repair of mesenchymal or epithelial neurological tissues by administering said agent. Described agent is an S100A8 protein, a cell which secretes an S100A8 protein, a vector into which DNA encoding S100A8 protein is inserted, an S100A9 protein, a cell which secretes an S100A9 protein or a vector into which DNA encoding an S100A8-9 protein is inserted.EFFECT: presented inventions can be used for inducing healing of injured tissues by recruiting bone-marrow-derived cells in area of damage, thereby treating such diseases as extensive pitting skin, bone fractures, cerebral infarction.7 cl, 44 dwg, 1 tbl, 9 ex

Use of structure for dna expression // 2598713
FIELD: medicine; biotechnology.SUBSTANCE: disclosed is use of a dumbbell-shaped linear, covalently closed DNA expression construct with a double-stranded stem and single-stranded loops located at both ends of stem, wherein stem of complementary deoxyribonucleic acids of a circular DNA strand comprises a promotor sequence, a coding sequence and a termination signal, where DNA construct codes TNF-α, for treating melanoma, wherein said DNA construct is administered by jet injection, and said construct is administered simultaneously or successively with vindesine.EFFECT: use of said DNA construct significantly enhances vindesine action.5 cl, 7 dwg, 1 tbl

odulation of antigen immunogenicity by deleting epitopes recognized by nkt-cells // 2598247
FIELD: biotechnology.SUBSTANCE: invention relates to biotechnology, specifically to prevention of undesired immune responses in mammals, and can be used in medicine. Method consists in (a) establishing at least one CD1d-binding motif of NKT cell epitope in peptide or polypeptide, wherein said epitope comprises the motif of [FWTHY]-X2X3-[ILMV]-X5X6-[FWTHY], wherein X2, X3, X5, X6 is any aminoacid, (b) removing said epitope by replacement of aminoacid residues in position P1 and/or P7 on non-hydrophobic residues; and (c) obtaining isolated peptide or a polypeptide with decreased ability to activate NKT cells in mammal.EFFECT: invention allows to reduce undesirable immune responses in mammals towards allofactors, towards viral vectors used for gene therapy and gene vaccination, towards proteins to which subjects are naturally exposed, towards genetically-modified organisms and towards undesirable effects related to vaccine administration for allergic or infectious diseases.10 cl, 3 dwg, 5 ex

Conjugates and compositions for immunotherapy and anticancer treatment // 2597989
FIELD: biotechnology.SUBSTANCE: invention refers to immunology, and can be used in medicine. Composition based on combined application of ApoA, interleukin 15 and Sushi domain alpha chain of IL15 receptor, is used for anti-tumour immune response in individual.EFFECT: use of ApoA1 together with IL15 and Sushi IL15ra domain provides synergetic effect on stimulating anti-tumour immune response in mammal by intensifying expansion of anticancer CTL.18 cl, 13 dwg, 13 ex

ethod for producing regulatory dendritic cells // 2597976
FIELD: biotechnology.SUBSTANCE: invention relates to biotechnology, specifically to obtaining regulatory dendritic cells, and can be used in medicine for treating diseases due to immunological anomalies and excess immune responses. Method comprises differentiation into regulatory dendritic cells, which can be induced in order to obtain regulatory dendritic cells, in presence of (S)-(+)-1-(5-hydroxy-1,5-dimethylhexyl)-3-[7-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl]urea, GM-CSF and IL-4 and subsequent ageing of regulatory dendritic cells in presence of TNF-α and/or LPS.EFFECT: higher quality and longer period of survival of patients during transplantation of said regulatory dendritic cells.10 cl, 2 dwg, 2 tbl, 4 ex

Treatment of alpha-l-iduronidase (idua) related diseases by inhibition of natural antisense transcript to idua // 2597972
FIELD: biotechnology.SUBSTANCE: invention relates to biotechnology, specifically to a method of increasing polynucleotide expression of alpha-L-Iduronidase (IDUA), and can be used in medicine. Invention also relates to identification of antisense oligonucleotides, which are targeted on natural antisense IDUA polynucleotide sequences chosen from SEQ ID NO: 2-9.EFFECT: invention increases polynucleotide expression of IDUA, which can be used for treating diseases and disorders associated with IDUA gene expression.39 cl, 5 dwg, 7 ex

Vectors and sequences for treating diseases // 2588667
FIELD: biochemistry.SUBSTANCE: described is nucleic acid molecule for gene therapy of mucopolysaccharidoses. Also described are vectors and pharmaceutical compositions for treating mucopolysaccharidosis disease.EFFECT: invention widens range of agents for treating mucopolysaccharidoses.15 cl, 15 dwg, 1 tbl, 11 ex

Novel peptides with analgesic effect, inhibiting asic-rfyfks // 2583299
FIELD: biotechnologies.SUBSTANCE: present invention relates to biotechnology, specifically to obtaining new recovered peptides, which cause analgesia and inhibit ASIC channels (proton-sensitive ion channels), to polynucleotides coding said peptides, as well as vectors and their application, and can be used in medicine. Above peptides allocated from poison of Dendroaspis polylepis snake and have amino acid sequence of LKCX4QHGKVVTCHRDMKFCYHNTGMPFRNLKLILQGCSSSCSETENNKCCSTDRCNK, wherein X4 denotes any amino acid; or sequence with similarity of at least 56 % with above sequence and preserving analgesic activity. EFFECT: invention allows to produce peptide inhibiting ASIC channels, containing at least one subunit, selected from group consisting of subunits ASIC1a and ASIC1b.14 cl, 7 dwg, 1 tbl, 7 ex

Low-molecular conjugates for intracellular delivery of nucleic acids // 2582235
FIELD: chemistry.SUBSTANCE: disclosed are compounds and compositions based thereon, used in medicine, of formulae and, a nucleic acid (II), where Y is -(CH2)3-; R1 is -(C1-6)alkyl; or -(CH2)m-phenyl, optionally substituted up to four times with a substitute selected from: -NO2, -CN, or a halogen; R2 is hydrogen; -(CH2)k-phenyl; -(C1-6)alkyl; -(CH2)k-C(O)-NH2; or -(CH2)k-N-C(Ph)3. The phenyl rings are optionally substituted with -O-(C1-4)alkyl; R3 is -NH-phenyl, wherein the phenyl is further substituted with a substitute independently selected from -(CH2)-OH or -(CH2)-O-C(O)-O-(4-nitrophenyl); k equals 1, 2, 3, 4, 5 or 6; m equals 1, 2, 3 or 4; and n equals 0 or 1, Ra is -(CH2)k-NH2; R1, wherein the nucleic acid is a single-stranded RNA oligonucleotide.EFFECT: novel compounds for nucleic acid delivery in cells and compounds for production thereof.10 cl, 653 ex, 19 tbl, 6 dwg

ethod of inducing cytotoxic anti-tumour immune response in vitro with using dendritic cells, transfected by rna tumour cells, to non-small cell lung cancer // 2578008
FIELD: biotechnologies.SUBSTANCE: invention can be used for inducing an antitumour immune response in vitro. Method involves production of adhesive and non-adhesive fractions of mononuclear cells (MNC) recovered from patient's peripheral blood, combined cultivation recovered from patient's peripheral blood MNC non-adhesive fraction with mature dendritic cells (DC), made from adhesive MNC fraction, transfected with RNA of tumour cells. Then, DC is subjected to stimulated ageing. Combined cultivation non-adhesive MNC fraction and transfected RNA autologous tumour cell DC is performed for 5 days. Note here that for producing mature DC after three days of cultivation of adhesive MNC fraction are transfected immature DC tumour RNA, and one day after transfection immature DC is for days stimulated ageing by adding a culture of immature DC tumour necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β) in the following proportions: TNF-α : IL-1β= 2.5:1.EFFECT: invention allows to effectively induce cytotoxic anticancer immune response to non-small cell lung cancer in vitro with the help of dendritic cells, transfected by RNA tumour cells.1 cl, 1 tbl

ethod of generating cytotoxic cells with activity against non-small cell lung cancer cells // 2577992
FIELD: biotechnologies.SUBSTANCE: invention relates to biotechnology, particularly to immunology, and can be used for generation of cytotoxic cells with activity against non-small cell lung cancer. Method involves combined cultivation in presence of recombinant human interleukine-12 and recombinant human interleukin-18, non-adhesive fraction of mononuclear cells (MNC) recovered from peripheral blood of patient with non-small cell lung cancer with dendritic cells obtained from monocytes of adhesive MNC fraction. To produce mature DC after three days of cultivation of adhesive MNC fraction, obtained immature DC are first co-cultivated for one day with tumour cell lysate non-small cell lung cancer with subsequent addition of TNF-α. During one day after loading lysate simultaneously with addition of proinflammatory cytokine TNF-α cytokine IL-1 is addedβ and matured loaded with lysate in presence of both cytokines.EFFECT: higher efficiency of generation of cytotoxic cells with activity against non-small cell lung cancer.1 cl, 1 tbl

System for stimulation of genes expression and vector containing said system // 2577971
FIELD: bioengineering.SUBSTANCE: claimed invention discloses a gene expression cassette. The latter contains the DNA-construct where the promoter, the gene, that should be expressed, and the sequence of poly A addition are bonded in such order. Besides, it contains the enhancer(s) or enhancer(s) with UAS doped with its part upstream of its transcription. The latter include at least one enhancer hTERT wherein the said enhancers with UAS are doped directly downstream of transcription from the sequence of poly A addition. The gene expression cassette is used in the procedures of gene expression and protein production coded by this gene as well as in preparations for the detection or treatment of diseases.EFFECT: increased expression of protein from the gene whereat the enhancer is added upstream of transcription from the promoter.18 cl, 75 dwg, 10 ex

ethod for identifying compounds for treating cancer // 2575828
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to oncology and concerns a complex containing a combination of polyinosinic-polycytidylic acid (pIC) and polyethylenimine (PEI), and using it as an agent for treating cancer, particularly melanoma.EFFECT: invention contains a pharmaceutical composition containing the complex applicable in treating melanoma, wherein the above complex induces autophagia in melanoma cells or in a cell line produced from the melanoma cells, and the above complex contains the combination of pIC and linear PEI in N/P ratio 1:5.10 cl, 1 tbl, 13 ex, 15 dwg

Obtaining of complexes of nucleic acids and cationic components cross sewed by disulfide bonds intended for transfection and immunostimulation // 2575603
FIELD: biotechnologies.SUBSTANCE: complex contains the polymeric carrier formed by the cationic components which are cross sewed by disulfide bonds where the cationic components cross sewed by disulfide bonds are cationic peptides, and the named disulfide bonds are formed by the cysteine residues which are comprised by cationic peptides localized near the terminal ends of cationic peptides, and the cargo molecule which at least one one-chained molecule of RNA.EFFECT: invention allows to perform efficient transfection of cells by nucleic acids both in vivo, and in vitro, and is intended for induction of congenital or adaptive immune response.10 cl, 15 dwg, 1 tbl, 1 ex
 
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