416 results about "Gene Modification" patented technology

Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of CRISPR systems and non-LTR retrotransposon elements.

Provided herein are compositions and methods for use in challenging pathogenic bacteria on plants. Optional features include modification of a donor bacteria to include exogenous nucleic acids encoding for conjugation machinery and gene modification components, such as guide sequence for use in CRISPR. The compositions and methods provided herein can be used for delivery to a wide variety of crops and for targeting one or more pathogens.

The invention discloses a production method of fucosylated oligosaccharide. The core of the method is as follows: the GDP-D-rhamnose is converted into the GDP-L-fucose by using the GDP-D-rhamnose-3, 5-epimerase; the GDP-D-rhamnose is obtained by converting the GDP-D-mannose-4, 6-dehydratase and the GDP-4-keto-6-deoxy D-mannose reductase by taking the GDP-D-mannose as a substrate, and the GDP-D-rhamnose is obtained by taking the GDP-D-mannose as a substrate. The invention relates to a method for producing a fucosylated oligosaccharide, which is characterized in that a GDP-D-mannose-4, 6-dehydratase, a GDP-4-keto-6-deoxyD-mannose reductase, a GDP-D-rhamnose-3, 5-epimerase and a fucosyltransferase are expressed in a genetically modified host cell, and the fucosylated oligosaccharide can be produced by the way mentioned above.

The invention discloses a construction method and application of a chlamydomonas reinhardtii-sourced high-sweetness protein variant engineering algal strain, the construction method comprises the following steps: carrying out gene modification on sweeteners Thaumatin and Brazzein, optimizing preference codons of chlamydomonas reinhardtii to synthesize CrThaumatin and CrBrazzein encoding genes, cloning the encoding genes into an expression vector pGM6, introducing the recombinant expression vector into a chlamydomonas reinhardtii wild-type chlamydomonas sp. Algal strain, and carrying out high-sweetness protein variant engineering algal strain of the chlamydomonas reinhardtii-sourced high-sweetness protein variant engineering algal strain of the chlamydomonas reinhardtii. And screening by using a paromomycin resistance marker carried by the expression vector to successfully obtain an engineering algal strain. According to the present invention, the engineering strain is subjected to fermentation production to obtain the dry and stable Chlamydomonas reinhardtii powder rich in the target sweet protein, and the protein purification oral test results show that the sweet taste of the Chlamydomonas reinhardtii powder is 3-5 times of the sweet taste of the natural Thaumatin and Brazzein protein;

The invention relates to pseudomonas putida engineering bacteria for producing rhamnolipid as well as a construction method and application of the pseudomonas putida engineering bacteria, the engineering bacteria take pseudomonas putida KT2440 with phaC1, phaC2, algD and fliC gene deletion as a chassis cell, and rhlAB, rmlACBD, algC and FabY genes are over-expressed in the chassis cell. Pseudomonas putida KT2440 with biological safety is used as a chassis cell for gene modification, the constructed engineering bacteria are used for fermentation production of rhamnolipid, on the basis of rhamnolipid yield increase, good physiological adaptability and fermentation stability are shown, and the rhamnolipid yield is increased. And the modified engineering strain can stably and efficiently produce rhamnolipid with a specific structure.

Provided herein are modified nucleic acids comprising modified MTM1 genes, modified muscle-specific promoters, e.g., MHCK7, or a combination thereof. Also provided herein are expression cassettes, AAV vector genomes, and AAV particles comprising the same. Further provided herein are methods of delivering MTM1 to a muscle cell and methods of treating XLMTM.

The invention relates to a gene modified cell for producing HMOs, which can be applied to synthesis of difucosyllactose, and belongs to the technical field of gene engineering. The invention provides a genetically modified cell, which contains an alpha-1, 2-fucosyltransferase polypeptide and a heterologous nucleic acid sequence of the alpha-1, 3-fucosyltransferase polypeptide. The genetically modified cell has higher activity of synthesizing difucosyllactose, and does not contain synthetic 3-fucosyllactose or lower side activity of synthetic 2 '-fucosyllactose. The technical scheme of the invention has positive significance for industrial production of human milk oligosaccharide, and the method is green, efficient and sustainable, is beneficial to industrial large-scale production, and has important practical value.

A genetically modified yeast cell, wherein the yeast cell comprises a genetic modification comprising overexpression of yeast gene encoding porphobilinogen deaminase (HEM3), the HEM3 gene having at least 80% identity with SEQ ID No. 7. The genome of the modified yeast cell further comprises one or more genetic modifications in one or more genes selected from: genes coding for heme-dependent repressor of hypoxic genes (ROX1), genes coding for heme oxygenase (HMX1), genes coding for a receptor for vacuolar proteases (VPS10), and genes coding for vacuolar proteinase (PEP4), the one or more genetic modifications being such that expression of a polypeptide from such a gene is reduced or disrupted or the polypeptide expressed is non-functional.

The application relates to a T cell-targeting nanoparticle based on a nucleic acid aptamer and a preparation method and application thereof, in particular to a T cell-targeting lipid aptamer, wherein the lipid aptamer comprises a hydrophobic molecule and a nucleic acid aptamer, the nucleic acid aptamer comprises at least one nucleic acid aptamer for targeting a T cell surface molecule, and the molar ratio of the hydrophobic molecule and the nucleic acid aptamer is 5000:1-1:10. The lipid aptamer or the nanoparticle formed by self-assembly technology of the lipid aptamer can realize cell 'pointing' gene modification and in-vivo gene reprogramming of cells.

Disclosed are CAR polypeptides comprising an antigen binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the intracellular signaling domain comprises a variant CD3 zeta (CD3ζ). Disclosed are nucleic acid sequences capable of encoding any of the disclosed CAR polypeptides. Disclosed are vectors comprising the nucleic acid sequence of the disclosed CAR nucleic acid sequences. Disclosed are cells comprising any of the CAR polypeptides, CAR nucleic acid sequences, or vectors disclosed herein. Disclosed are methods of treating a subject having cancer comprising administering a therapeutically effective amount of a composition comprising a T cell genetically modified to express one or more of the CAR polypeptides disclosed herein to the subject having cancer. Disclosed are methods of using one or more of the disclosed CAR polypeptides.

Provided herein are recombinant microorganisms that express a subject polypeptide. Microorganisms can comprise an expression construct comprising a flagellin promoter operatively linked with a heterologous nucleotide sequence encoding the subject polypeptide. The flagellin promoter sequence can comprise a genetic modification that reduces CsrA inhibition of translation. Microorganisms also can comprise a genetic modification that reduces FlgM inhibition of SigD initiation of transcription. The target polypeptide can be an aldehyde dehydrogenase. Such microorganisms are useful in the treatment of alcohol hangover.

The invention relates to a stem cell pretreatment technology in the field of biomedicine, which is characterized in that stem cells are pretreated in a specific parameter window (10-80mu g / mL, 5-60min and 36-38 DEG C) by establishing an ozone concentration-time-temperature cooperative control model, so that the anti-apoptosis ability, homing efficiency and paracrine function of the stem cells are remarkably enhanced. The method breaks through the technical bottleneck of low survival rate of traditional stem cell transplantation, and avoids the carcinogenic risk of gene modification. The application covers the three fields of myocardial repair, liver regeneration and nerve injury, and the special culture medium and the kit developed in a matched manner realize standardized operation. The survival rate of the pretreated stem cells after transplantation is increased by more than two times, the VEGF secretion amount is increased by 150%, and a safe and efficient new treatment strategy is provided for clinic.

The invention concerns homogenous antibody-conjugates with high payload loading (high DAR) obtained by site-specific conjugation to a single antibody N-glycan. The conjugates according to the invention are homogeneous, i.e. have a DAR at or close to the theoretical DAR with a narrow distribution, and do not require any genetic modification of the antibody. The invention further concerns a modular, non-genetic preparation method for such conjugates, involving three simple steps and starting from any antibody. These steps are (a) enzymatic remodeling of the glycan to give an antibody functionalized with two or four click probes per antibody, (b) strain-promoted cycloaddition with a multivalent, bifunctional reagent comprising one cyclic alkyne and at least two click probes that are not reactive towards the cyclic alkyne, and (c) inverse electron-demand Diels-Alder cycloaddition of the click probes with branched linker-drug constructs comprising one cyclic alkyne or strained alkene, connected to one or more payloads preferably connected through a cleavable linker. The resulting conjugates, with DAR6 or higher, are rapidly generated with high homogeneity and with surprising stability. In addition, HIC profiles of the resulting ADCs indicate small relative retention time and therefore show high potential in the targeting of tumour cells and / or the treatment of cancer.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes a survival factor, wherein the genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor.

Genetically modified zebrafish, in which mutation combinations frequently identified in human AML are stably expressed in the stem cell population of the fish, are provided. The combination of mutations result in morphologic, cytochemical and molecular changes of its blood cells that are remarkably similar to those in human AML. The zebrafish model provides a foundation for the study of AML initiation and progression and a high throughput in vivo drug screening platform to identify personalized therapies for AML based on specific mutation combinations. The method of drug screening includes contacting embryos or adult fish containing mutations as disclosed herein, with a test agent, at test concentrations and test intervals to determine the therapeutic effect if any, of the test agent.

This disclosure generally relates to methods and compositions for functional genetic modifications at selected genomic sites, such as the FGF21 gene or the GDF15 gene. This disclosure further provides compositions and methods for genomic editing of AU-rich elements in the FGF21 and / or GDF15 genes for treating obesity-related diseases and disorders.

The present disclosure relates to deoxyribonucleic acid (DNA) editing agents, and their use in preparing genetically modified cells and birds. The present disclosure further relates to fertile genetically modified avians and genetically modified avian primordial germ cells (PGCs) for producing sterile genetically modified avians (birds) that can serve as surrogate hosts for donor PGCs. The present disclosure further relates to methods for producing fertile avian strains that can produce a population of embryos and offspring, in both sexes, all of which are sterile and viable, and further relates to their subsequent use as sterile surrogate hosts for donor PGCs.

Disclosed is a genetically modified rodent, in which an immunoglobulin light chain locus is modified to insert a human immunoglobulin light chain gene segment. The rodent is capable of normal reproduction and of producing antibodies containing human light chains. Further provided are a method for preparing the genetically modified rodent and the use.

The present invention provides an AutoCell Platform (ACP), an advanced, fully automated, functionally closed system designed to revolutionize the manufacturing of genetically modified cell therapies. This innovative platform integrates automation, closed-loop processing, and novel technologies to address the inefficiencies and high costs of traditional methods. Key features include automated centrifugal seeding for enhanced genetic modification efficiency, microbubble-assisted cell selection for precise cell isolation, and a modular design for scalable amplification across clinical and research environments. By reducing production timelines from 30-40 days to less than 3 days and orders of magnitude in cost, the ACP enables instant manufacturing, decentralization, and broader accessibility. Advanced quality control measures and standardized design ensure compliance and consistent therapeutic outcomes. The ACP supports a variety of applications from CAR-T therapies to regenerative medicine, representing a transformative leap in global accessibility of precision medicine and life-saving cell therapies.

The present invention relates to a T cell receptor (TCR) that specifically binds to a KRAS_G12V mutant antigen, a fusion protein or complex containing a TCR, a nucleic acid encoding a TCR, genetically modified cells containing the same, and a method for producing genetically modified cells. The present invention also relates to enhancing T cell function by coexpressing an exogenous CD8 molecule and a TCR gene in T cells. The present invention provides uses of the TCR and genetically modified cells in the detection, prevention, and / or treatment of cancers associated with the KRAS_G12V mutant antigen.

Disclosed herein are genetically engineered Kluyveromyces marxianus cells capable of producing D-allulose with increased talitol formation. The engineered cell may comprise a genetic modification resulting in overexpression of a native talitol dehydrogenase enzyme; an exogenous polynucleotide sequence encoding an allulose-6-phosphate 3-epimerase enzyme at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to at least one of SEQ ID NOs:249-256, 258, and 259; and an exogenous polynucleotide sequence encoding an allulose-6-phosphate phosphatase enzyme at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to at least one of SEQ ID NOs:87, 89, 190, 123, 105, 107, 115, 83, 95, 113, 117, 119, 121, 127, 131, 137, 145, 169, 173, 179, and 183.

The present invention discloses a genetically modified rodent whose immunoglobulin light chain locus is modified so as to comprise a single rearranged human immunoglobulin light chain gene V / J gene upstream of a mouse Kappa light chain locus constant region, a mouse variable region sequence cannot bind to an endogenous constant region to form a complete mouse light chain antibody, the rodents are capable of normally reproducing and producing human light chain-containing antibodies. The invention also provides a method of making the genetically modified rodent and a use of the rodent.

Genetically modified mice whose immunoglobulin loci are engineered to be inserted into gene segments of human immunoglobulin variable regions are disclosed, the mice being capable of normal reproduction and producing human-mouse chimeric antibodies comprising a human variable region and a mouse constant region. The invention also provides a method for preparing the genetically modified mouse and application of the mouse.

To provide a gene modified cell including a modified T cell receptor (TCR) alpha steady region gene in a genome of the gene modified cell.SOLUTION: There is provided a gene modified cell including in a genome thereof, a modified human T cell receptor (TCR) alpha steady region gene, the modified human TCR alpha steady region gene includes, from 5' to 3', a 5' region of the human TCR alpha steady region gene, an exogenous polynucleotide, and a 3' region of the human TCR alpha steady region gene. The modified human TCR alpha steady region gene is a gene modified human T cell or a gene modified cell derived from a human T cell, and in comparison with a non-modified control cell, expression of an endogenous TCR on a cell surface is suppressed.SELECTED DRAWING: Figure 1

The present application relates to the field of microbial technology, and particularly relates to a gene editing method of propionibacterium acnes VB208 and application thereof. Propionibacterium acnes ) on February 20, 2023, and is preserved in the China General Microbiological Culture Collection Center, with a preservation number of CGMCC No.26576. The propionibacterium acnes screened by the present application has the characteristics of skin surface occupation, high conversion efficiency, gene modification potential and efficient expression of exogenous proteins, and can be used as an engineering strain. Furthermore, a genetic operation system suitable for the strain can be established by using the propionibacterium acnes, and the application prospect is wide.

The process provided in this invention transfects primary cells with gene editing reagents using a high-volume gas-permeable cell culture device and a flow-through electroporation device under conditions that improve gene editing performance, cell yield, and drug (DP) quality characteristics for cell therapy applications. As demonstrated in the examples, primary cells edited according to the process provided herein achieved improved double-strand break (DSB) formation rates, increased frequency of homology-directed repair (HR) and non-homologous end joining (NHEJ) combinations, increased frequency of bi-allelic and mono-allelic HR events, improved cell viability, proliferative capacity, and cell fitness after gene editing, and reduced manufacturing time.

The present disclosure relates to the use of a maltose dependent degron to control stability of a protein of interest fused thereto at the post-translational level. The present disclosure also relates to the use of a maltose dependent degron in combination with a maltose-responsive promoter to control gene expression at the transcriptional level and to control protein stability at the post-translational level. The present disclosure also relates to the use of a stabilization construct that couples expression of a cell-growth-affecting protein with the production of non-catabolic compounds. The present disclosure further relates to the use of a synthetic maltose-responsive promoter. The present disclosure further provides compositions and methods for using a maltose dependent degron, a maltose-responsive promoter, and a stabilization construct, either alone or in various combinations, for the production of non-catabolic compounds in genetically modified host cells.

The invention provides genetically modified non-human animals that express chimeric human / non-human MHC I polypeptide and / or human or humanized β2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.