7244results about "Active genetic ingredients" patented technology

To provide a medicine for treating a disease in a mammal.SOLUTION: Provided is a medicine for treating a disease in a mammal, comprising an expression cassette that is a first expression cassette comprising a chimeric gene operably linked to a first expression control element, the chimeric gene comprising a first portion comprising a minigene having an alternatively spliced exon and a second portion encoding a first RNA encoding a protein, the first portion being 5' to the second portion, the second portion lacking an initiation codon or start codon, the alternatively spliced exon comprising a translation initiation regulatory sequence, expression of the protein being controlled by inclusion of the alternatively spliced exon, and the medicine being used in combination with a small molecule splicing modifier that modulates splicing of the alternatively spliced exon.SELECTED DRAWING: Figure 1

The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-freeze drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry 10 powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

The invention provides a modified TnpB-omega RNA gene editing system and application of the modified TnpB-omega RNA gene editing system. In particular, the present invention provides a modified TnpB related [omega] RNA skeleton. The modified omega RNA skeleton provided by the invention has at least three stem-loop structure fragments, and has a shorter length and a compact structure than a natural omega RNA skeleton, so that the modified omega RNA skeleton and TnpB can be jointly carried in a single AAV vector, the administration efficiency is improved, and high-efficiency gene editing is realized.

The invention provides an artificial nucleic acid molecule which is used for improving the expression quantity of target amino acid, polypeptide or protein. The artificial nucleic acid molecule at least comprises a target 5'untranslated region (UTR), a target coding region (CDS) and a target 3 'untranslated region (UTR). Wherein the sequence of the target 5 'UTR is one of the following sequences: 5' UTR of a high-expression gene and a 5 'UTR variant of the high-expression gene. The sequence of the target 3 'UTR is one of the following sequences: 3' UTR of a high-expression gene and a 3 'UTR variant of the high-expression gene. Optionally, the artificial nucleic acid molecule may further comprise, for example, a 5 '-end cap structure (Cap), a PolyA tail. The 5 'UTR and the 3' UTR have regulating effects on translation and stability of nucleic acid molecules, so that the 5 'UTR, the 3' UTR and variants thereof are selected from high-expression genes, the nucleic acid molecules can be further stabilized and are not easy to degrade, and the amount of protein or polypeptide obtained by translation of the nucleic acid molecules can be increased. The invention also provides methods for making, delivering, and using such artificial nucleic acid molecules, as well as the use of the artificial nucleic acid molecules for the treatment and / or prevention of related diseases or disorders.

The invention provides an UTR (Untranslated Region) element H2202 P1-G as well as a construction method and application thereof, and relates to the technical field of mRNA (messenger ribonucleic acid). According to the present invention, the ribosome load prediction and the secondary structure optimization are performed on the natural 5 'UTR of the HIV TAT 202 gene through the BaidleHelix platform, and the obtained HTAT 202 P1 sequence avoids the inhibitory hairpin structure so as to significantly improve the luciferase expression quantity compared to the natural UTR; an ncRNA sequence without a secondary structure is introduced on the basis of the HTAT 202 P1, translation inhibition of a 5 'cap region is further relieved, and the protein expression quantity of the constructed H2202 P1-G mutant (the DNA sequence of the H2202 P1-G is as shown in SEQ NO 1, and the RNA sequence is as shown in SEQ NO 2) is further improved.

The invention relates to methods of modulating immune cells in a patient by altering microbiota of the patient. The invention also relates to methods of modulating treatments or therapies in a subject organism by altering microbiota of the subject. The invention also relates to cell populations, systems, arrays, cells, RNA, kits and other means for effecting this. In an example, advantageously selective targeting of a particular species in a human gut microbiota using guided nucleic acid modification is carried out to effect the alteration.

The invention provides an UTR element NHP1 as well as a construction method and application thereof, and relates to the technical field of mRNA. A 5 'UTR with a good expression effect is designed by integrating dominant sequences of a human high-expression gene and a pathogen natural UTR, a chimeric structure NHP1 with high ribosome load is predicted through a calculation model, a DNA sequence of the NHP1 is as shown in SEQ NO 1, and an RNA sequence of the NHP1 is as shown in SEQ NO 2; an EGFP report system is adopted on the DNA level to rapidly screen UTR; the translation efficiency is quantitatively evaluated on the RNA level through luciferase mRNA (N1-methyl pseudouridine modification); and the particle size is controlled by a microfluidic technology, so that the optimized UTR-mRNA is efficiently expressed after being delivered.

The disclosure relates to compositions and methods for the preparation, use, and / or formulation of adeno-associated virus capsid protein variants.

Provided herein are lentiviral vectors comprising a mutated, heterologous envelope protein, a targeting protein, and at least one transgene for delivery to and expression by a cell characterized by the targeting protein. Also provided are methods and materials for producing the lentiviral vectors described herein, methods for transducing target cells, and cells transduced by lentiviral vectors according to the present disclosure.

The present invention relates to T lymphocytes targeting CLD18A2 and a preparation method and application thereof. The inventors have successfully found a target gene CLD18A2 suitable for developing CAR T cells from a number of tumor-related genes for the first time, and successfully prepared CAR T cells targeting CLD18A2, thereby providing a new treatment method for pancreatic cancer, gastric cancer and other tumors.

The invention relates to the field of gene therapy, in particular to an RBM25 gene epigenetics activation technology based on a CRISPR / dCas9-SunTag system and application of the RBM25 gene epigenetics activation technology in ischemic heart failure treatment, the RBM25 gene epigenetics activation technology comprises the following steps: (a) protein containing inactivated Cas9 (dCas9) fused with a plurality of GCN4 peptide repetitive sequences, the number of the GCN4 peptide repetitive sequences is 8-12, and the dCas9 contains D10A and H840A double mutations; (b) a protein containing fusion of an anti-GCN4 single-chain antibody fragment (scFv) and a TET1 catalytic structural domain; (c) at least one gRNA of a target RBM25 gene promoter region, wherein a target sequence of the gRNA is selected from a sequence as shown in SEQ ID NO: 1-3; and (d) a lipid nanoparticle (LNP) system for delivery of said (a), (b), and (c).

This disclosure provides improved RNA molecules, including mRNA molecules that can be produced by in vitro transcription and are suitable for in vivo transfection using an appropriate delivery vehicle, such as a lipid nanoparticle (LNP) or targeted lipid nanoparticle (tLNP). The improved RNA include particular combinations of 5' untranslated region (UTR) and 3' UTR, particular 3' UTRs, or particular open reading frame sequences. Also provided herein are compositions of the LNP, or tLNP with an antibody as a targeting moiety, such as anti-CD8 antibodies that are used as targeting moiety.

The invention relates to methods, uses, systems, arrays, engineered nucleotide sequences and vectors for inhibiting bacterial population growth or for altering the relative ratio of sub-populations of first and second bacteria in a mixed population of bacteria. The invention is particularly useful, for example, for treatment of microbes such as for environmental, medical, food and beverage use. The invention relates inter alia to methods of controlling microbiologically influenced corrosion (MIC) or biofouling of a substrate or fluid in an industrial or domestic system.

The present disclosure provides compositions and methods comprising recombinant particles suitable for specifically delivering one or more chimeric antigen receptors to immune effector cells in vivo.

In various embodiments, the disclosure provides compositions, such as polypeptides, polynucleotides, gene editing systems, small molecules, vectors, or host cells, comprising and / or modulating the expression or activity of an immunomodulatory-related protein, such as a cytokine. In various embodiments, the disclosure also provides methods of treating inflammation, aging, senescence, fibrosis, autoimmunity, cancer, infection, and / or immunological disease using agents comprising and / or modulating the expression or activity of an immunomodulatory-related protein, as well as methods of identifying the agents.

The invention provides a UTR (Untranslated Region) sequence for improving mRNA (Messenger Ribonucleic Acid) stability and translation efficiency and application of the UTR sequence, and particularly provides an mRNA molecule which comprises a coding region for coding polypeptide or protein and a fragment thereof, a 5 'UTR sequence positioned at the upstream of the coding region and / or a 3' UTR sequence positioned at the downstream of the coding region, the 5 'UTR sequence is a nucleotide sequence as shown in SEQ ID NO: 1, and the 3' UTR sequence is a nucleotide sequence as shown in SEQ ID NO: 2; and / or, the 5 'UTR sequence is a nucleotide sequence as shown in SEQ ID NO: 3, and the 3' UTR sequence is a nucleotide sequence as shown in SEQ ID NO: 4. According to the present invention, the mRNA stability and the translation efficiency are improved through the new and optimized UTR sequence, and the UTR sequence can be used as the element for enhancing the RNA expression efficiency in the nucleic acid treatment drug or the mRNA vaccine so as to provide more and better choices for the mRNA therapy.

This disclosure provides improved RNA molecules, including mRNA molecules that can be produced by in vitro transcription and are suitable for in vivo transfection using an appropriate delivery vehicle, such as a lipid nanoparticle (LNP) or targeted lipid nanoparticle (tLNP). The improved RNA include particular combinations of 5′ untranslated region (UTR) and 3′ UTR, particular 3′ UTRs, or particular open reading frame sequences. Also provided herein are compositions of the LNP, or tLNP with an antibody as a targeting moiety, such as anti-CD8 antibodies that are used as targeting moiety.

The purpose of the present invention is to provide a lipid composition capable of delivering a nucleic acid such as RNA to a hematopoietic stem / progenitor cell or a mesenchymal stem cell, and a method for delivering a therapeutic agent to a cell using the lipid composition. The present invention provides a lipid composition comprising (A) a therapeutic agent and (B) a lipid nanoparticle conjugated to a targeting molecule wherein the lipid nanoparticle comprises an ionizable lipid and the targeting molecule specifically binds to a marker of hematopoietic stem / progenitor cells or mesenchymal stem cells.

The invention relates to methods, uses, systems, arrays, engineered nucleotide sequences and vectors for inhibiting bacterial population growth or for altering the relative ratio of sub-populations of first and second bacteria in a mixed population of bacteria. The invention is particularly useful, for example, for treatment of microbes such as for environmental, medical, food and beverage use. The invention relates inter alia to methods of controlling microbiologically influenced corrosion (MIC) or biofouling of a substrate or fluid in an industrial or domestic system.

The disclosure is directed in part to variant capsid polypeptides that can be used to deliver payloads.

Compositions and methods are provided herein for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and / or targeted mutagenesis. The compositions include fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incorporated into the target DNA molecule.

The present disclosure provides compositions and methods useful in the treatment of trinucleotide repeat disorders, including Huntington's disease and Friedreich's ataxia. The present disclosure also provides gRNAs designed to target the HTT or FXN genes. Complexes comprising a base editor and any of the gRNAs disclosed herein are also provided by the present disclosure. The present disclosure further provides polynucleotides, vectors, cells, compositions, and kits. Methods of treating Huntington's disease and Friedreich's ataxia are also provided herein.

The present disclosure provides methods and compositions comprising Cas TypeV programmable nucleases and lipid nanoparticles capable of delivering the Cas TypeV programmable nucleases and genome editing systems comprising same.

The disclosure is directed in part to variant capsid polypeptides that can be used to deliver payloads.

Disclosed herein are molecules and pharmaceutical compositions that induce an insertion, deletion, duplication, or alteration in an incorrectly spliced mRNA transcript to induce exon skipping or exon inclusion. Also described herein include methods for treating a disease or disorder that comprises a molecule or a pharmaceutical composition that induces an insertion, deletion, duplication, or alteration in an incorrectly spliced mRNA transcript to induce exon skipping or exon inclusion.

The invention relates to application of an MYZAP overexpression vector in preparation of a medicine for preventing and treating MIRI, and belongs to the technical field of biological medicine. In order to solve the problem that application of gene drugs in prevention and treatment of myocardial ischemia reperfusion injury is limited, the invention provides application of an MYZAP gene overexpression recombinant vector in preparation of drugs for prevention and treatment of myocardial ischemia reperfusion injury, and the MYZAP gene overexpression recombinant vector is an adeno-associated virus vector AAV9-MYZAP for overexpressing MYZAP. Experiments prove that MYZAP overexpression can improve the cardiac function after myocardial ischemia reperfusion, reduce the occurrence rate of arrhythmia and improve the functions of sodium ion channels, potassium ion channels and calcium ion channels of myocardial cells. On the basis, the invention further provides a medicine for preventing and treating myocardial ischemia reperfusion injury, a new strategy is provided for gene therapy of myocardial ischemia reperfusion injury, and the medicine has a wide clinical application prospect.

The invention provides a hypoglycemic peptide which is prepared by taking bovine whey protein as a raw material and is stable in gastrointestinal digestion and absorption. In an in-vitro cell experiment, the peptide fragment can improve the uptake of insulin-resistant HepG2 hepatocytes and synthesize glycogen by using glucose, can promote intestinal endocrine cells NCI-H716 to secrete GLP-1, has a certain synergistic effect, and can further play the effects of promoting GLP-1 secretion and activating a GLP-1 receptor through combined use. An insulin resistance mouse model is constructed by utilizing high-fat diet, and the peptide fragment is adopted for intervention, so that the hypoglycemic peptide is further proved to have obvious effects on losing weight, reducing lipid accumulation and assisting in reducing blood fat, and meanwhile, the hypoglycemic peptide can be used for improving insulin resistance related symptoms. The milk peptide provided by the invention has gastrointestinal digestion stability and hypoglycemic activity, can be used as a functional milk base material for developing food, medicines or health care products with the effect of regulating blood sugar, and is wide in application prospect.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a macrophage Angulin-1 gene and / or an Angulin-1 protein in preparation of medicines and diagnostic products for preventing and / or treating atherosclerosis and related diseases. Research finds that plaque and necrotic core areas of an atherosclerosis animal model are remarkably increased due to macrophage Angulin-1 gene knockout, and disease development is promoted; and the recovery of the expression level of Angulin-1 significantly inhibits the development of lesion. Cell experiments show that Angulin-1 reduces intake of oxidized low-density lipoprotein by down-regulating expression of macrophage LOX-1, so that formation of foam cells is inhibited. Therefore, the macrophage Angulin-1 can be used as an atherosclerosis drug target, a gene therapy target gene and an auxiliary diagnosis marker, and a new theoretical basis and an intervention strategy are provided for prevention and treatment of the disease.