3838results about "Vectors" patented technology

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

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

The invention relates to the field of prevention and treatment of respiratory diseases, and discloses a preparation method of a human respiratory syncytial virus preventive mRNA vaccine. The main components of the mRNA vaccine comprise mRNA for coding an antigen and lipid nanoparticles. According to the mRNA sequence provided by the invention, an independently researched and developed 5 'UTR / 3' UTR sequence and a codon optimization mode are adopted, and efficient translation of target protein can be realized. According to the mRNA vaccine provided by the invention, RSV F protein is selected as an antigen, and the RSV F protein sequence is optimally designed, so that stable pre-fusion conformation RSV F protein can be expressed, and after a mouse is immunized, the mouse can be induced to generate high-level RSV F protein specific binding antibody titer and neutralizing antibody titer.

Disclosed herein are compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

The invention provides compositions and methods for manufacturing adoptive cell therapies. In particular embodiments, the invention provides methods of harvesting populations of cells, isolating and activating PBMCs, expanding T cells, and administering the T cell therapeutic to a subject in need thereof.

Polynucleotides, vectors, systems of vectors or polynucleotides, cells, and methods for expressing AAV Rep and Cap proteins are provided. In certain aspects, these polynucleotides, cells, and methods may produce higher levels of one or both of Rep and Cap transcripts. In some aspects, these polynucleotides, cells, and methods may produce higher levels of one or both of Rep and Cap proteins. In various aspects, these polynucleotides, vectors, systems of vectors or polynucleotides, cells, and methods use one or more heterologous polyA sequences with one or both of the Rep and Cap coding sequences. In numerous aspects, these polynucleotides, vectors, systems of vectors or polynucleotides, cells, and methods may use one or more enhancers to increase expression of Rep proteins, where such enhancers can be transcriptional enhancers, translational enhancers, or combinations thereof. In certain aspects, these polynucleotides, vectors, systems of vectors or polynucleotides, cells, and methods may be used to produce recombinant AAV (rAAV).

According to the invention, a structural domain reaction substrate sequence consisting of Exon1 (E1), P1 and Exon2 (E2) sequences of ribozyme is mutated, and E1, P1 and E2 sequences are mutated under the condition of maintaining the structural stability, so that the Azoarcus group I intron ribozyme still has enzyme activity and can maintain the capability of forming circular RNA (Ribose Nucleic Acid). The invention discloses a flexible vector construction method for preparing circular RNA (Ribonucleic Acid) without limitation of a substrate sequence, which comprises the following steps: determining a target to-be-cyclized site sequence NNUNNNN, and segmenting the target to-be-cyclized site sequence NNUNNNN into E1: NNU and E2: NNNN; with E1 and E2 sequences as references, designing IGS sequences to respectively form complementary pairing with E1 and E2; and 5'and 3 'homologous arms, IRES, CDS and other elements are respectively added. The method provided by the invention can be used for preparing the circular RNA for any target sequence, has no residual sequence, and has relatively high cyclization efficiency. The FlexCirc cyclization system designed on the basis of Azoarcus group I intron ribozyme can form the circular RNA, the cyclization substrate sequence has the characteristic of flexible design, and the cyclization efficiency can realize a relatively high cyclization proportion.

Proposed are recombinant entomopathogenic bacteria transformed using promoter replacement technique, a preparation method, and uses thereof for producing pesticides and controlling pests. Provided are recombinant entomopathogenic bacteria in which the promoter of the GXP synthase gene (gxpS gene) is replaced in the entomopathogenic bacteria with an arabinose inducible promoter using a promoter replacement technique. The recombinant entomopathogenic bacteria prepared in the present disclosure can produce large quantities of GXPs, which acts to suppress immunity of pests, by controlling the expression of the GXP synthetase gene (gxpS gene) through an addition of an inducer. The recombinant entomopathogenic bacteria prepared in the present disclosure can also effectively control pests through a response that suppresses the immunity of pests.

The invention provides an engineered nuclease with high salt tolerance. The polypeptide comprises one or more mutations, so that the three-dimensional structure of the polypeptide has more surface areas with positive charges. Compared with the nuclease with the SEQ ID NO: 1 sequence, the polypeptide still has at least 60% nuclease activity under the condition that the solution ion strength exceeds 200 mM.

Disclosed are AAV viral-based vector compositions useful in delivering a variety of nucleic acid segments, including those encoding therapeutic polypeptides to selected mammalian host cells for use in therapeutic autoimmune modalities, including, for example, the in vivo induction of immunological tolerance via a liver-directed AAV-based gene therapeutic regimen for treating and / or ameliorating autoimmune disorders such as multiple sclerosis. Further disclosed are nucleic acid segments encoding therapeutic polypeptides that have been codon-optimized for expression in human cells.

The invention discloses an mRNA (messenger ribonucleic acid) transcription skeleton vector and application thereof in preparation of a self-amplification type mRNA vaccine, and belongs to the technical field of veterinary biological products. According to the invention, alphavirus non-structural protein regions NSP2 and NSP3 of a self-amplification type mRNA skeleton are modified, a polyA tail is optimized, and a novel self-amplification type mRNA skeleton is constructed; the self-amplification type mRNA vaccine can improve the antigen expression efficiency, reduce the toxicity of non-structural protein to cells and improve the encapsulation efficiency and delivery efficiency by combining with the optimization of the components and proportion of a lipid nano delivery system, and meanwhile, the self-amplification type mRNA vaccine is wide in applicable pathogen antigen range and can be popularized to more animal epidemic diseases. The characteristics of high-efficiency expression, low-toxicity delivery and single-dose immunization are expected to renovate the immunization strategy of the existing animal vaccine, the epidemic prevention cost of the breeding industry is reduced, and the method has a wide industrial application prospect.

This invention is directed to treatment of a subject having or suspected of having a cancer comprising administering to the subject a monoclonal antibody and NK-92 expressing Fc receptor.

The present invention relates to pluripotent stem cell comprising an expression construct for expression of a CEBPα protein and an expression construct for expression of an ADIG protein. The invention further provides for methods of producing adipocytes comprising the pluripotent stem cells and for foodstuff comprising the adipocytes or pluripotent stem cells.

A printed circuit board according to an embodiment comprises: an insulating layer; a circuit pattern disposed on the upper surface of the insulating layer; a support layer which is disposed on the upper surface of the insulating layer to expose the upper surface of the circuit pattern and is in contact with the sides of the circuit pattern; and a protective layer disposed on the upper surfaces of the support layer and the circuit pattern, wherein the upper region of the insulating layer comprises a first region and a second region, and the protective layer comprises an open region exposing the upper surfaces of the support layer and the circuit pattern that are disposed in the first region, and the support layer comprises a first upper surface positioned at the highest level among the upper surfaces of the support layer and a second upper surface positioned at the lowest level among the upper surfaces of the support layer, the second upper surface being lower than the first upper surface, and the protective layer comprises a first portion which contacts the upper surface of the circuit pattern of the first region and a second portion which contacts the upper surface of the support layer of the first region, and the second portion of the protective layer contacts the second upper surface of the support layer and includes a first lower surface which is lower than the upper surface of the circuit pattern.

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

The invention provides a targeting vector and a method for targeting a host cell, the vector comprises a first molecule combined with an endocytosis receptor of a target cell and a second molecule for promoting release of a substance carried by the targeting vector into cytoplasm, when the targeting vector is a virus vector, the first molecule is not a part of a virus envelope protein, and the second molecule is not a part of a virus envelope protein. The second molecules promote endosome escape or lysosome escape of the targeting carrier. According to the present invention, the first molecule is designed according to the endocytosis receptor of the to-be-targeted cell so as to target different types of cells, and after the vector is subjected to reasonable mutation, the infection of the cells not requiring the targeting can be avoided, and the accuracy of the vector can be improved.

The present disclosure relates to compositions, methods, processes, kits and devices for selecting, designing, preparing, manufacturing, formulating and / or using polynucleotides having internal ribosome entry site (IRES) sequences, IRES-like sequences, or combinations thereof. In particular, the present disclosure relates to compositions, methods, processes, kits and devices for selecting, designing, preparing, manufacturing, formulating and / or using cyclic polynucleotides (e.g., cyclic RNAs). The present disclosure also relates to methods of improving expression, functional stability, immunogenicity, ease of manufacture and / or half-life of therapeutic products encoded by the circular RNA.

Compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic coronavirus proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.

The invention discloses mRNA, an mRNA-LNP vaccine of the mRNA, a preparation method and application of the mRNA-LNP vaccine. The invention discloses an H5 subtype avian influenza virus vaccine, and aims to provide a vaccine which combines a mosaic sequence with an mRNA vaccine, achieves a good effect in an immune protection experiment of chickens, and can realize cross protection of branched strains of H5 subtype avian influenza virus 2.3. 4.4b and 2.3. 4.4 hours. According to the technical scheme, the nucleotide sequence of the mRNA is as shown in SEQ ID NO. 1; the nucleotide sequence of the mRNA is a Mosaic sequence which is obtained by designing a gene sequence of a 2.3. 4.4b branch strain of the avian influenza H5N6; the mRNA-LNP vaccine comprises mRNA (Messenger Ribonucleic Acid) with a nucleotide sequence as shown in SEQ ID NO. 1; belongs to the technical field of biology.

Provided herein are methods of inserting a nucleic acid encoding a polypeptide of interest into a target genomic locus in a cell or a population of cells in a subject, methods of expressing a polypeptide of interest from a target genomic locus in a cell or a population of cells in a subject, methods of treating an enzyme deficiency in a subject in need thereof, and methods of preventing or reducing the onset of a sign or symptom of an enzyme deficiency in a subject in need thereof. The methods use CD40 inhibitors (e.g., CD40 antigen-binding molecules) to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting.

The present invention relates to methods and compositions for reducing the immunogenicity of chimeric Notch receptors, and specifically to transcription factors useful for controlling gene expression delivered to tissues by such chimeric Notch receptors.

Disclosed herein are antibodies or antigen-binding fragments thereof that specifically bind to human CD19. Chimeric antigen receptors and chimeric antigen receptor transgenes comprising an antigen binding domain that specifically binds to human CD19 are also disclosed. Also described herein are immune cells, viral vectors, and other compositions containing the antibodies, the antigen binding fragments, the chimeric antigen receptors, and / or the chimeric antigen receptor transgenes.

The invention belongs to the technical field of strain metabolism modification, and particularly relates to a streptomyces avermitilis strong promoter and application. The nucleotide sequence of the streptomyces avermitilis strong promoter provided by the invention is as shown in SEQ ID NO. 4. The strong promoter can express and regulate a key gene, and the mRNA relative expression level of the gene driven by the strong promoter can still be kept stable in the 48-96-hour growth stage of the streptomyces avermitilis, which indicates that the strong promoter can keep high activity in the 48-96-hour growth stage of the streptomyces avermitilis, so that the target gene can be stably and highly expressed. Therefore, the strong promoter can be used for constructing recombinant plasmids for expressing key genes for synthesizing target natural products and streptomyces avermitilis recombinant bacteria, and the constructed streptomyces avermitilis recombinant bacteria can efficiently produce the target natural products.

The invention belongs to the fields of gene engineering, bioengineering and biological medicine, and relates to a nucleic acid molecule for coding human defensin, a method for preparing the human defensin and application. The nucleic acid sequence of the nucleic acid molecule comprises any one of the following sequences: (1) a sequence as shown in SEQ ID NO.2; (2) a nucleic acid sequence for coding human defensin, which is obtained by substituting, deleting or adding one or more than two nucleotides to the sequence as shown in SEQ ID NO.2; and (3) a nucleotide sequence which has at least 80% sequence homology with the nucleotide sequence in (1) or (2) and has the same or similar functions with the nucleotide sequence in (1) or (2). According to the method provided by the invention, the recombinant expression vector is constructed by using nucleic acid molecules for coding the human defensin, the human defensin hBD-3 can be recombined and expressed, the recombinant fusion protein is released to the supernatant of a culture solution, the protein purification is convenient, the obtained recombinant human defensin has a tissue regeneration function, and a new active molecule is provided for the development of a novel drug.

The invention discloses a human albumin binding peptide 1E3 and application of the human albumin binding peptide 1E3 in promoting purification of human albumin, and belongs to the technical field of polypeptides. The human albumin binding peptide comprises an amino acid sequence as shown in SEQ ID NO. 1; and / or an amino acid sequence of a fusion protein with the same function, which is obtained by connecting tag protein to the N terminal and / or C terminal of the amino acid sequence as shown in SEQ ID NO.1. The human albumin binding peptide has extremely high affinity with human albumin and can be used for separating and purifying a human albumin solution, and the purity of the purified human albumin far exceeds the pharmacopoeia standard and can reach 99.99% or above. The method is good in safety and stable in process, and has a wide application prospect in the aspect of separation and purification of the human albumin.

The present disclosure provides compositions for targeting trans-splicing of an mRNA precursor in a cell and methods of using the same.

Provided herein are methods of inserting a nucleic acid encoding a polypeptide of interest into a target genomic locus in a cell or a population of cells in a subject, methods of expressing a polypeptide of interest from a target genomic locus in a cell or a population of cells in a subject, methods of treating an enzyme deficiency in a subject in need thereof, and methods of preventing or reducing the onset of a sign or symptom of an enzyme deficiency in a subject in need thereof. Some methods, such as when a subject has preexisting against an immunogen to be administered, use plasma cell depleting agents or combinations comprising plasma cell depleting agents to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting. Other methods, such as when a subject has no preexisting immunity against an immunogen to be administered, use B cell depleting agents (e.g., anti-CD20xCD3 antibody or functional fragment thereof) to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting.

The present disclosure relates, generally, to compositions and methods for producing, purifying, and using circular RNA.