399 results about "Reprogramming" patented technology

The invention provides an enhancer RNA (Ribonucleic Acid) molecule MZGAe1 and application thereof, and relates to the technical field of biology. The invention provides an enhancer RNA (Ribonucleic Acid) molecule MZGAe1. The nucleotide sequence of the enhancer RNA molecule MZGAe1 is as shown in SEQ ID NO: 1; meanwhile, the invention further provides a specific sgRNA sequence for activating the molecule in a targeted manner and a recombinant vector of the specific sgRNA sequence. Expression of endogenous MZGAe1 of cells is specifically activated by adopting a CRISPR activation technology, and conversion of mouse embryonic stem cells to bicellular-like cells can be efficiently promoted. By providing a brand-new endogenous targeted MZGAe1 accurate activation tool, the efficient transformation of wild mouse embryonic stem cells to bicellular cells can be realized only under the condition of endogenous activation of single enhancer RNA molecule MZGAe1, the proportion is at least increased by 5%, the expression of a totipotent marker gene ZSCAN4 is activated, and the expression of the totipotent marker gene ZSCAN4 is promoted. And an efficient and specific brand-new research tool and scheme are provided for researching zygote genome activation, embryonic development early events and cell reprogramming.

The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for example through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein (e.g., a eukaryotic target protein such as a mammalian target protein or a fungal target protein or a prokaryotic target protein such as a bacterial target protein). These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of intracellular target proteins. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of the targeted protein's activity. In some embodiments, the compounds of the invention “re-program” the binding of the presenter proteins to protein targets that either do not normally bind to the presenter protein (e.g., do not show detectable binding in mammalian cells absent the compound). In some embodiments, provided compounds “re-program” presenter protein binding to greatly enhance interaction with a particular target with which it may have some interaction absent the compound. Interactions achieved through such reprogramming result in an ability to modulate the activity of these new targets.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a (e.g., ocular disease), preventing a disease (e.g., ocular disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof).

Disclosed are methods of augmenting efficacy of oncology therapies by providing reprogrammed cells such as personalized regenerative cells that modulate the tumor microenvironment. In one embodiment, somatic cells are dedifferentiated into OCT-4 expressing cells and endowed with tumor homing properties through culture or gene engineering. Once a stable population of tumor homing cells is established, such cells are made to express immune stimulating agents constitutively, or selectively upon entering the cancer microenvironment. Selective expression of immune stimulatory agents can be induced by exposure to hypoxia, acidosis, immune suppressive signaling or inflammatory signaling.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a (e.g., ocular disease), preventing a disease (e.g., ocular disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof).

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof in the central nervous system or ex vivo. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a disease (e.g., a neurological disease), preventing a disease (e.g., neurological disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof.

Provided are a liver precursor cell and a construction method therefor and the use thereof. The method for constructing liver precursor cells comprises the steps of: S0, providing liver precursor cells, a mixed solution and a reprogramming culture medium, wherein the mixed solution comprises a serum-free culture medium, polyethyleneimine and a CLP plasmid; S1, carrying out a transfection treatment on the liver precursor cells and the mixed solution to obtain transfected liver precursor cells; and S2, placing the transfected liver precursor cells into the reprogramming culture medium for subculture to obtain immortalized liver precursor cells. The method solves the problems that in the prior art, liver precursor cells cannot be transformed into immortalized cell strains by means of immortalizing genes and cannot be continuously passaged in vitro.

The present invention relates to a method for producing reprogrammed cells from somatic cells without gene introduction. The method comprises: (a) culturing somatic cells in a medium containing a histone deacetylase inhibitor; and (b) culturing the cells cultured in step (a) in a medium containing an OCT3 / 4 transcription stimulating factor to produce reprogrammed cells.

The invention belongs to the technical field of triple negative breast cancer, and particularly relates to application of a polypeptide capable of specifically blocking phosphorylation of metabolic enzyme PSAT1S337 and functional remodeling of PSAT1 in preparation of a triple negative breast cancer treatment product. The phosphorylated polypeptide targeting PSAT1S337 is designed, and it is found that the polypeptide obviously inhibits growth of triple negative breast cancer tumors and can improve the curative effect of anti-PD-1 immunotherapy at the animal level. Meanwhile, the invention further provides application of the reagent for detecting the phosphorylation level of the PSAT1S337 and / or the hydroxylation level of the GPX4P159 in preparation of products for diagnosing and prognosing the triple negative breast cancer. The invention discloses a molecular mechanism of functional remodeling of the serine metabolic enzyme PSAT1 in occurrence and development of cell ferroptosis and triple negative breast cancer, and provides a new thought and an effective scheme for research and development of anti-tumor drugs for targeted serine metabolism reprogramming and early diagnosis of tumors.

The invention belongs to the technical field of cell small molecule compound reprogramming and bone tissue engineering material culture, and discloses a method for inducing fibroblasts to be reprogrammed into osteoblasts. According to the invention, small molecule compounds act on fibroblasts, each small molecule is endowed with characteristics of a set of characteristic gene expression mode, and the small molecules are divided into different modules according to the expression characteristic mode, so that the fibroblasts of the cells are converted into osteogenic differentiation, the osteogenic differentiation effect is enhanced and maintained, and the in-vivo development of the cells is simulated to a great extent; therefore, healthy osteoblasts can be prepared from the skin fibroblasts, cell stress pressure can be resisted, and the prepared cells are free of tumorigenicity, safe and healthy. The osteoblast disclosed by the invention can be applied to preparation of bone materials and medicines for treating bone defects, for example, the osteoblast and a traditional bone material are used for constructing an active bone tissue engineering material, so that the use of allogeneic bones commonly used in clinic at present is avoided, and the occurrence of adverse ethical events is reduced.

The invention provides a preparation method and a kit for reprogramming induced pluripotent stem cells of PBMC (peripheral blood mononuclear cells), particularly provides PBMC reprogramming based on mRNA-LNP (peripheral blood mononuclear cells), and more particularly relates to a preparation method for reprogramming induced pluripotent stem cells of peripheral blood mononuclear cells. The preparation method comprises the following steps: preparing a nano liposome mRNA (messenger ribonucleic acid) cocktail-LNP; according to the method, the nano-liposome mRNA-LNP is used for inducing peripheral blood mononuclear cells to reprogram, so that reprogrammed induced pluripotent stem cells are obtained, and an iPSCs reprogramming technology which is low in cost, low in toxicity, efficient, stable, repeatable and safer is realized. The invention also provides a reprogramming kit and a preparation method of the induced pluripotent stem cells.

Provided herein are methods and related compositions for enhancing or enhanced partial reprogramming of target cells in a subject in need thereof (e.g., a human subject suffering from or at risk of a disease), the method comprising administering a plurality of mesenchymal lineage progenitor or stem cells (MLPSCs), exosomes derived therefrom, or conditioned culture media derived therefrom to a subject that expresses or will express one or more reprogramming factors in a population of target cells, whereby a plurality of the target cells in the subject become partially reprogrammed, but not fully reprogrammed.

The present invention relates to novel lipid nanoparticles capable of liver-specific delivery of mRNA, a manufacturing method therefor, and a liver disease therapeutic agent capable of regenerating the liver by liver-specific delivery of the bio-reprogramming factor mRNA using same. The lipid nanoparticles according to the present invention allow for liver-specific delivery of mRNA at very high efficiency, and the lipid nanoparticles that encapsulate the mRNA-based bio-reprogramming factor mRNA are specifically delivered to liver tissues of an individual requiring liver regeneration to induce short-term expression, thereby easily setting the dose and expression period of a therapeutic agent, leading to a significant reduction in side effects of a therapeutic agent for liver regeneration using an existing cell reprogramming factor.

The invention discloses a medicine composition for inducing fibroblasts to be reprogrammed into pericyte-like cells (PCLCs) through a chemical small molecule combination, and the medicine composition is used for treating sepsis. According to the invention, a chemical reprogramming strategy without genetic modification is adopted, an endogenous signal channel is activated through a time sequence, and fibroblasts from somatic cells are efficiently converted into PCLCs with high expression of genes such as EMILIN3, LAMC3, GDF10, AHR, CD109, AHR, NQO1, QPRT and the like. When applied to treatment of sepsis, the medicine composition can improve pathological symptoms and reduce death rate by synergistically exerting anti-inflammatory, anti-oxidation, immune regulation and tissue barrier protection effects. The invention provides a novel safe treatment strategy based on non-genetically modified cells for sepsis.

The invention relates to a culture medium for inducing hypoderm stem cells and application thereof, and belongs to the technical field of stem cells. The invention provides a culture medium for inducing hypoderm stem cells. The culture medium for inducing the hypoderm stem cells comprises the following components: a platelet-derived growth factor AA (PDGFAA), a leukemia inhibition factor (LIF), a fibroblast growth factor 4 (FGF4), a GSK-3alpha / beta inhibitor CHIR99021, a TGF-beta I type receptor inhibitor A83-01 and a bone forming protein 4 (BMP4). The culture medium for inducing the hypoderm stem cells can accurately regulate and control the activity of key signal channels such as NODAL, BMP, WNT, FGF and JAK / STAT in the somatic cell reprogramming process, and ensures that the somatic cells maintain the characteristics of the hypoderm stem cells in the reprogramming process so as to support self-renewal and hypoderm lineage induction of the somatic cells in the reprogramming process; therefore, the fate transformation from the somatic cells to the hypoderm stem cells is realized.

Engineered or non-naturally occurring systems and compositions comprising novel Type V Cas polypeptides and orthologs thereof are disclosed herein. Also provided are methods of use for the novel Type V Cas polypeptide systems and compositions for reprogrammable targeting of nucleic acid and polynucleotide components.

The invention belongs to the technical field of anti-tumor, and discloses application of HP and ICT combined anti-PD-1 inhibitor hydrogel in residual cancer recurrence after IRFA. The excellent drug delivery capacity of the hydrogel system is utilized, and the in-vivo local slow release effect of ICT and BMS202 can be remarkably amplified. Through synergistic treatment of the TAN and the MDSC, local and whole body adaptive immunoreactions can be efficiently activated, TAN is effectively reprogrammed to be in a tumor suppression type, infiltration of PMN-MDSC is reduced, and the conclusion is verified in a plurality of mouse tumor models in the chapter. Therefore, the HP (at) ICT / BMS provides a promising delivery strategy for improving the sensitivity of anti-PD-L1 treatment and efficiently preventing and treating latent residual cancer and metastasis after IRFA operation.

A preparation method and applications of rejuvenated and regenerative fibroblasts, where the rejuvenated and regenerative fibroblasts are prepared from normal fibroblasts by inhibiting the JAK-STAT signaling pathway. The rejuvenated and regenerative fibroblasts are prepared by treating the target cells with a small molecular combination, a cytokine combination or a recombinant protein combination. This application further provides an application of the rejuvenated and regenerative fibroblasts in the reprogramming or rejuvenation of cells, tissues, organs and organisms.

The present invention relates in part to nucleic acids encoding proteins, nucleic acids containing non-canonical nucleotides, therapeutics comprising nucleic acids, methods, kits, and devices for inducing cells to express proteins, methods, kits, and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, and therapeutics produced using these methods, kits, and devices. Methods for inducing cells to express proteins and for reprogramming and gene-editing cells using RNA are disclosed. Methods for producing cells from patient samples, cells produced using these methods, and therapeutics comprising cells produced using these methods are also disclosed.

The invention discloses an overexpression YTHDC2 macrophage and a pharmaceutical application of the overexpression YTHDC2 macrophage. The overexpressed YTHDC2 macrophage disclosed by the invention is obtained by modifying and reprogramming a YTHDC2 gene. The medicine application comprises an application of the overexpressed YTHDC2 macrophage in preparation of a medicine for killing breast cancer cells; the invention relates to application of overexpressed YTHDC2 macrophages in preparation of breast cancer cell targeting drugs. The invention relates to application of overexpressed YTHDC2 macrophages as a drug carrier for targeting breast cancer cells. Compared with the prior art, the expression quantity of the YTHDC2 gene of the overexpressed YTHDC2 macrophage is 5 times higher than that of the common macrophage, and the overexpressed YTHDC2 macrophage shows an M1 type anti-tumor phenotype. The obvious effects of targeting and killing breast cancer cells are realized.

The present disclosure is directed to a method of generating a population of neurons. This method involves providing a population of human glial progenitor cells: providing a recombinant genetic construct comprising (i) a promoter and / or enhancer for a gene which is selectively or specifically expressed by human glial progenitor cells, and (ii) a nucleic acid sequence encoding one or more neuronal reprogramming factors for producing neurons from glial progenitor cells, where the nucleic acid sequence is operably linked to the 3′ end of said promoter and / or enhancer to achieve expression of the one or more neuronal reprogramming factors; transfecting cells of the glial progenitor cell population with the recombinant genetic construct; and culturing the population after said transfecting under conditions suitable for neuron production from the transfected glial progenitor cells of the population. Also disclosed are methods of inducing the production of neurons, as well as recombinant genetic constructs.

The present invention discloses a preparation method and application of a bacterial bionic vesicle for reprogramming macrophages. The preparation of the bacterial bionic vesicle is to first fuse the bacterial outer membrane anchor protein with the IFN-γ gene, and then use high-pressure homogenization technology to drive genetically engineered bacteria to extrude from the cracks and self-assemble into bacterial bionic vesicles modified with IFN-γ surface. In vitro, the bacterial bionic vesicles of the present invention can promote the reprogramming of M1 macrophages into M2 macrophages, and release nitric oxide to directly kill tumor cells. In vivo, the bacterial bionic vesicles can efficiently enrich in the tumor area by virtue of their nanosize, reprogram the tumor-promoting M2TAMs to the tumor-killing M1TAMs and coordinate adaptive immunity to jointly inhibit tumor growth. In short, the bacterial bionic vesicles of reprogramming macrophages of the present invention are a powerful immunomodulator, which significantly inhibits tumor growth in a variety of tumor models and is of great significance in the immunotherapy of tumors.

Systems, methods and compositions for targeting polynucleotides are detailed herein. In particular, engineered DNA-targeting systems comprising IscB polypeptides, novel IscB nucleases and reprogrammable targeting nucleic acid components and methods and application of use are rovided.

The invention relates to a compound. The compound comprises a polysaccharide conjugate, an anti-PD-L1 monoclonal antibody and a PKM2 inhibitor. The compound disclosed by the invention can be accumulated and retained in tumor tissues, so that dendritic cells are effectively stimulated to be mature, an inhibitory immune microenvironment is relieved, and a specific anti-tumor immune response is initiated. The expression of PKM2 can be effectively inhibited, so that glycolysis in tumor tissues is inhibited, and a more favorable environment is provided for infiltrating the tumor tissues with T lymphocytes. The compound disclosed by the invention is expected to enhance the treatment effect of RFA on advanced HCC patients by reprogramming iRFA-induced tumor immunosuppression, and has huge potential in the aspect of improving prognosis of the advanced HCC patients treated by the RFA.

The present invention relates to a complex comprising a polysaccharide conjugate, an anti-PD-L1 monoclonal antibody, and a PKM2 inhibitor. The complex of the present invention can accumulate and remain in tumor tissue, effectively stimulate dendritic cell maturation, alleviate the inhibitory immune microenvironment, and trigger a specific anti-tumor immune response. It can effectively inhibit the expression of PKM2, thereby inhibiting glycolysis in tumor tissue and providing a more favorable environment for T lymphocytes to infiltrate tumor tissue. The complex of the present invention is expected to enhance the therapeutic effect of RFA on patients with advanced HCC by reprogramming iRFA-induced tumor immunosuppression, and has great potential in improving the prognosis of patients with advanced HCC treated with RFA.

The present invention belongs to the field of nanomedicine technology, and specifically relates to an iron metabolism disruptor and its application. The present invention provides an iron metabolism disruptor that can be used for tumor iron metabolism treatment. The present invention also provides a para-apoptosis inducer that can induce para-apoptosis in tumor cells and enhance immunotherapy. The novel iron metabolism disruptor gallium sulfide nanodots obtained by the present invention reprogram the iron metabolism axis by releasing H2S and releasing Ga 3+ Replacing Fe sites has the dual functions of "reprogramming" and "interfering" with iron metabolism pathways. GaS nanodots disrupt tumor cell iron metabolism, induce para-apoptosis, and modulate macrophage phenotype, enhancing tumor therapy.

The invention discloses a composition for inducing functional ciRPE cells through chemical reprogramming, an induction method and application. The invention provides a two-step chemical reprogramming strategy, and fibroblasts can be transdifferentiated into functional RPE (ciRPE) cells through an eye domain (EF) / optic bubble (OV) intermediate state. The ciRPE cells are very similar to natural RPE cells in structure and function, have no tumorigenic risk after being transplanted to the retina of an RD rat, can be integrated into host tissues, effectively protect photoreceptor cells and remarkably recover the visual function.

The invention provides a myocardial cell reprogramming method, a related preparation and application. The invention provides a myocardial cell reprogramming method which comprises the following steps: carrying out balling culture on myofibroblasts on bionic interpenetrating network hydrogel, so that the myofibroblasts are gathered, and reprogramming the myofibroblasts into myocardial-like cells. The myofibroblasts used before culture are in an activated state. According to the method for realizing cell reprogramming based on the bionic interpenetrating network hydrogel, cell nucleus transplantation, virus transfection or gene editing are not needed, additional chemical induction reagents are not needed, the safety is high, and the effect is remarkable. And culturing supernate based on the reprogrammed cell balls for treating myocardial fibrosis.

The present invention relates in part to nucleic acids, including nucleic acids encoding proteins, therapeutics and cosmetics comprising nucleic acids, methods for delivering nucleic acids to cells, tissues, organs, and patients, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, therapeutics, and cosmetics produced using these methods, kits, and devices. Methods and products for altering the DNA sequence of a cell are described, as are methods and products for inducing cells to express proteins using synthetic RNA molecules, including cells present in vivo. Therapeutics comprising nucleic acids encoding gene-editing proteins are also described.

The invention provides an anti-inflammatory chimera, a reprogramming macrophage and a preparation method and application thereof, and belongs to the technical field of cell therapy. The anti-inflammatory chimera provided by the invention is a chimera based on conversion from an inflammatory signal to an anti-inflammatory signal, and can convert an inflammatory signal of a diseased region of a fibrosis disease into an IL-10 signal, so that the problem of an inflammatory environment of a fibrosis tissue is solved, and steady-state balance of the tissue is promoted. Moreover, the chimera is introduced into the recovery type macrophage, the recovery type phenotype stability of the recovery type macrophage is enhanced, and the purposes of improving the inflammatory environment of the diseased region of the fibrotic disease, reducing fibrotic cell activation, continuously degrading an extracellular matrix, swallowing dead cells and remodeling diseased tissues are achieved. In addition, the invention provides a preparation method of the reprogramming macrophage and a specific application of the reprogramming macrophage in fibrotic tissues.