214 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.

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 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 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 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.

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 belongs to the technical field of biological medicines, and particularly discloses a pH and ultrasound double-response type oncolytic microorganism as well as a preparation method and application thereof. On the basis of a tumor targeting platform, a mild thermal response gene loop expression GM-CSF and a surface-coated oncolytic microbial system are integrated, chemotherapeutic drugs are released in a tumor core area, and immunogenic cell death is induced. A thermal response loop is accurately activated through low-intensity focused ultrasound, and engineering bacteria are promoted to express GM-CSF and secrete a large amount of mannose modified OMVs. Due to the nanometer size and mannose targeting of the OMVs, the OMVs are efficiently enriched in lymph nodes, the OMVs are reprogrammed into an immune activation state from an immune tolerance state, and the OMVs and ICD cooperate to promote dendritic cell maturation, tumor antigen presentation and activation of tumor killer T cells, so that a remarkable and powerful treatment effect is achieved in various tumor models, and the application prospect is wide. A new strategy is provided for remodeling the lymph node immune microenvironment and enhancing the anti-tumor immune response.

Provided herein are T cell receptor (TCR) fusion proteins (TFPs) that contain a CD70-binding domain, T cells engineered to express one or more TFPs, antibodies that specifically bind to CD70, and methods of their use for the treatment of diseases, including cancer.

There is provided a mutant KLF protein that can induce reprogramming of a somatic cell at a higher efficiency than a KLF protein having a natural amino acid sequence. There is also provided a method for efficiently producing an iPS cell by using the mutant KLF protein. There is provided a mutant KLF protein having an amino acid substitution, or a peptide fragment thereof containing the amino acid substitution.

The invention discloses a method for inducing fibroblasts to be reprogrammed into mesenchymal matrix-like cells (MLCs) by using small chemical molecules and application of the mesenchymal matrix-like cells (MLCs) in the anti-aging field. The invention discloses a set of specific chemical small molecule composition and an induction scheme thereof, which can be used for efficiently reprogramming fibroblasts from somatic cells into MLCs. Furthermore, the huge potential of the MLCs obtained by the method in anti-aging research is deeply explored, and the effect of the MLCs is proved to be obviously superior to that of umbilical cord mesenchymal stem cells in the aspects of reversing cell aging phenotypes and recovering tissue functions. The invention not only provides a new stem cell source strategy for avoiding the ethical and safety problems of the traditional reprogramming technology, but also lays a solid cell foundation for developing a novel, safe and effective anti-aging therapy based on cell transplantation or secreted factors.

The invention discloses an application of a DHA-RXR-PPAR signal channel in promotion of postoperative recovery of hysteromyoma after HIFU (high intensity focused ultrasound). Clinical sample metabolic spectrum analysis and in-vitro cell function experiments are combined, and research proves that the differential metabolite DHA drives macrophage metabolism reprogramming through an RXR-PPAR signal axis, so that the macrophage is promoted to be transformed into an anti-inflammatory and phagocytosis-promoting repair phenotype, the absorption and repair process of the HIFU postoperative hysteromyoma is accelerated, and the treatment effect of the HIFU postoperative hysteromyoma is improved. A new intervention target spot (RXR-PPAR gamma axis) and a new potential medicine are provided for HIFU (high intensity focused ultrasound) postoperative rehabilitation.

The invention discloses a method for constructing astrocytes serving as a smoke disease model, and belongs to the technical field of crossing of stem cells and neuroscience. The method comprises the following steps: S1) reprogramming CD34 + cells in in-vitro PBMCs (peripheral blood mononuclear cells) of smoke disease patients carrying and not carrying RNF213p.R4810K mutation to obtain induced pluripotent stem cells; and S2) directionally inducing and differentiating the induced pluripotent stem cells into astrocytes through a neural progenitor cell way, wherein the obtained astrocytes are the astrocytes capable of being used as the smoke disease model. The astrocyte model prepared by the invention can be used for researching pathogenesis, nerve-blood vessel interaction process and blood-brain barrier (BBB) related functions of smoke diseases, and can be further applied to molecular typing of diseases and in-vitro function evaluation of candidate drugs.

Methods of treating a patient in need thereof are described herein. In some embodiments, the method comprises disposing a TGFb-receptor 1 inhibitor within a biological compartment of the patient, and disposing a lymphotoxin beta receptor (LTBR) agonist within the biological compartment of the patient. In some instances, the patient has cancer. In some cases, the cancer is pancreatic cancer, or more specifically pancreatic ductal adenocarcinoma. In tertiary lymphoid structures (TLS)-resistant tumors, the disposing of the TGFb-receptor 1 inhibitor within the biological compartment of the patient results in a reprogramming of fibroblast phenotype and overcomes resistance to generation of TLS in tumors of the patient.

The application provides a reprogramming vector for blood cells and application thereof. Through the technical scheme in the disclosure, a low-cost and high-benefit solution can be provided for efficient reprogramming and application of iPSCs, and the wide application of iPSCs in clinical and scientific research fields is significantly promoted, and the iPSCs have important application value and development potential in research and practice in aspects such as disease models, drug screening, cell therapy and the like.

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

A method for reprogramming native CD4+ T-cells is provided. The method comprises incubating the CD4+ T-cells with a Class 1 HDAC inhibitor for a period of time sufficient to increase cytotoxicity of the CD4+ T-cells in comparison to the cytotoxicity of native CD4+ T-cells. The method may be utilized to prepare cytotoxic tumor infiltrating CD4+ T-cells for use to treat cancer, including MHC-I deficient cancers.

The invention relates to a mouse liver cancer cell P1-Hepa1-6 capable of simulating human liver cancer metabolism reprogramming characteristics and application thereof, and belongs to the technical field of biotechnology and medicine. The invention provides a mouse liver cancer cell P1-Hepa1-6 which is preserved in the China Center for Type Culture Collection on November 12, 2025, the preservation address is Wuhan University, Wuhan, China, and the preservation number is CCTCC NO: C202586. The invention further provides a preparation method of the mouse liver cancer cell P1-Hepa1-6. The mouse liver cancer cell P1-Hepa1-6 has the advantages that the mouse liver cancer cell P1-Hepa1-6 can be used for preparing the mouse liver cancer cell P1-Hepa1-6; the mouse liver cancer cell P1-Hepa1-6 has high malignant phenotype, can simulate human liver cancer metabolism reprogramming characteristics, is high in pertinence and good in repeatability, and has important application value and market prospect in the fields of liver cancer basic research, drug target discovery, preclinical efficacy evaluation and the like.

Plant cell fate and development is altered by treating cells with cellular reprogramming factors. Embryogenesis inducing embryogenesis factor genes and / or morphogenic developmental genes are used as cellular reprogramming factors, specifically comprising polypeptides or polynucleotides encoding gene products for generating doubled haploids or haploid plants from gametes. Maize microspores treated by contacting the isolated cells with an exogenous purified, recombinant embryogenesis inducing embryogenesis factor gene products and / or morphogenic developmental gene polypeptide results in embryogenesis. The gametes of a maize plant develop into embryoids when transformed with a genetic construct including regulatory elements and structural genes capable of acting in a cascading fashion to alter cellular fate of plant cells. Embryogenesis factor proteins and / or developmental morphogenic proteins expressed from a genetic construct are used for ex situ treatment methods and for in planta cellular reprogramming.

The invention relates to the technical field of medicinal chemistry, and particularly discloses application of echinacoside in preparation of a medicine for improving autism social and cognitive impairment, and the application comprises the following steps: constructing a recombinant saccharomyces cerevisiae strain, and knocking out a precursor competition pathway gene; performing metabolic flow reprogramming fermentation on the recombinant strain; centrifuging the fermentation liquor at 7000-9000 r / min and pretreating the fermentation liquor with an 8-12 kDa ultrafiltration membrane; carrying out dual-targeting affinity chromatography purification on the pretreatment liquid; the preparation method comprises the following steps: preparing echinacoside into a liposome containing pH sensitive poly-histidine; and adding a freeze-drying protective agent into the suspension to carry out gradient pre-freezing and vacuum freeze-drying. According to the application, a mode of combining recombinant saccharomyces cerevisiae strain construction and metabolic flow reprogramming fermentation is adopted, targeted enrichment of echinacoside is realized through affinity chromatography coupled with autism brain region specific double ligands, then the echinacoside is prepared into the liposome containing pH sensitive poly-histidine, the double ligands are modified, and the effects of precise targeting and efficient effect are achieved.

This invention discloses the application of the Six2 gene in promoting the reprogramming of fibroblasts into muscle stem cells, belonging to the field of biotechnology. The nucleotide sequence of the Six2 gene is shown in SEQ ID NO.1, and the fibroblasts are chicken fibroblasts. This invention uses chicken embryonic fibroblasts as the reprogramming target, and induces the reprogramming of chicken embryonic fibroblasts into muscle stem cells by overexpressing the Six2 gene, promoting the expression of stem cell-related genes MyoD, MyoG, Myf5, and Pax7. The circ_TCONS / gga-miR181-5p / Six2 regulatory network participates in the reprogramming process; it improves the efficiency of somatic cell reprogramming into stem cells, greatly promotes the application of reprogramming, and provides a new approach for the sustainable acquisition of muscle stem cells.

Provided are a method of overexpressing a target gene and / or a method of reprogramming cells, the method including steps of (a) introducing a vector into cells, into which vector a promoter and a target gene are inserted; and (b) applying an electromagnetic wave to the cells obtained in the step (a), and a method of treating a disease using the method.When the method of overexpressing a target gene using the electromagnetic wave-reactive promoter of the present disclosure is used, it is possible to artificially regulate expression levels of desired target genes in a simple manner in vivo and in vitro and to regulate expression of the target genes until a desired predetermined time.

The invention relates to the technical field of cell differentiation, in particular to an ovarian granular cell exosome preparation method and system based on cell directional differentiation, and the method comprises the following steps: reprogramming starting material cells to obtain initial induced pluripotent stem cells, carrying out cell identification to obtain induced pluripotent stem cells, and carrying out directional differentiation on the induced pluripotent stem cells to obtain the ovarian granular cell exosome. Obtaining an ovarian granular cell cluster, obtaining a culture supernatant, purifying the culture supernatant to obtain an initial exosome, carrying out quality detection on the initial exosome to obtain a detection result, if the detection result is that the detection does not reach the standard, obtaining an adjusted exosome, taking the adjusted exosome as the initial exosome, and taking the adjusted exosome as the initial exosome. And returning to the step of detecting the quality of the initial exosome until the detection result is that the detection reaches the standard, and confirming the initial exosome as the target exosome when the detection result is that the detection reaches the standard. The problem that the purity of the exosome is low in the preparation process of the ovarian granular cell exosome at present can be solved.

Disclosed is an efficient and non-genetically modified iPSC-induced, industrialized single clone selection platform, and a use. The platform can efficiently perform reprogramming, and only requires the use of a minimal number of reprogramming factors (OCT4, SOX2, E6, E7). During the single clone separation stage of the present invention, SSEA4 / TRA-1-60 is used as a screening marker, and a large number of single cell clones are obtained by means of flow cytometry. The platform described in the present invention has advantages such as high reprogramming efficiency, high safety, easy operation, and large-scale production.

The present invention provides improved and / or shortened processes and methods of reprogramming TILs to make therapeutic TIL populations with increased therapeutic efficacy. Such reprogrammed TILs can be used in therapeutic regimens.

The application discloses a method for inducing T cell reprogramming into NK-like cells, comprising the following steps: (1) culturing the T cells in a culture system to obtain activated T cells; (2) adding small molecule inducers twice to the activated T cells to obtain NK-like cells; wherein the culture system in step (1) contains 1-10 v / v % serum substitute and / or platelet lysate, and does not contain fetal bovine serum. By optimizing the culture process and precisely adding drugs twice, the small molecule accumulation toxicity caused by multiple drug additions is avoided, the damage to the structure and function of the mitochondrial membrane is reduced, the mitochondrial membrane potential is significantly improved, the energy metabolism capacity of the mitochondria is enhanced, sufficient energy support is provided for the long-term survival and function maintenance of the cITNK cells, and the physiological activity of the cells is ensured from the energy metabolism level.

This useful solution, in the field of biotechnology and regenerative medicine, relates to a process for enhancing the efficiency of induced pluripotent stem cell (iPSC) colony formation from human peripheral blood mononuclear cells (PBMCs). The solution aims to overcome the low reprogramming efficiency, unstable colony formation, and limited iPSC cloning rates commonly encountered in PBMC iPSC generation processes. The technical essence of the solution lies in the synchronized optimization of the reprogramming process, including pre-activating PBMCs with an appropriate cytokine combination at predetermined times before reprogramming, using a non-integrated Sendai virus system under optimized transformation conditions, switching culture media at defined intervals to promote cell state transitions, and applying a selection, enrichment, and stabilization process for iPSC cloning in the initial passages after colony formation.The process also incorporates cell line quality control steps through assessment of residual Sendai virus RNA removal and mycoplasma contamination testing during line maintenance. Experimental results show that the proposed process increases the number of iPSC colonies formed, improves the rate of establishing stable iPSC lines, and enhances cell homogeneity and pluripotency maintenance. The solution can be applied in basic research, pathogenesis modeling, drug screening, regenerative medicine, and studies using induced pluripotent stem cells derived from human peripheral blood cells.

The application discloses a composition for inducing T cell reprogramming into NK-like cells and application thereof. The composition comprises a DNA methyltransferase inhibitor, a histone deacetylase inhibitor and a vitamin C phosphate derivative; the molar ratio of the DNA methyltransferase inhibitor and the vitamin C phosphate derivative is 1: (40-2500); and the final concentration of the histone deacetylase inhibitor is 0.05-2 muM. The vitamin C phosphate derivative is used to replace common vitamin C, and the defects of common vitamin C, such as weak reprogramming promotion effect in a platelet lysate system, limited cell proliferation and low receptor expression, are overcome, so that the composition is more suitable for a clinical serum-free large-scale preparation scene.

The present application relates to the technical field of biological medicine, and particularly relates to application of fullerenol in preparation of tumor prevention or treatment drugs for inducing trained immunity. The present application finds that fullerenol can induce formation of trained immunity, activate immune reprogramming of bone marrow hematopoietic stem cells, produce long-term pro-inflammatory phenotype, form persistent immune memory, and further enhance functions of innate immune cells. It is verified by experiments that fullerenol can significantly inhibit tumor growth in an animal model without obvious systemic toxicity; epigenetic remodeling of bone marrow hematopoietic stem cells can be sustained for several weeks to several months, and has long-acting anti-recurrence potential. In addition, trained immunity induced by fullerenol can be used for immune regulation of various solid tumors, and fullerenol is simple in synthesis, can be produced on a large scale, has excellent biocompatibility and stability. Therefore, the present application has wide application prospect.

The application discloses a kind of compositions and applications for regenerating retinal ganglion cells by using endogenous microglia.The present application finds that multiple genes (Brn3b, Sox2, Cbln1 and NP1, referred to as BSCN) can be expressed in microglia to transform into retinal ganglion cells by in vivo microglia fate lineage tracking.The regenerated ganglion cells project axons to the distant brain, rebuild visual neural circuit and restore impaired vision in adult glaucoma mice.In addition, the regenerated ganglion cells can stably survive for up to one year, and the same regeneration strategy is used in old glaucoma mice, which confirms the effectiveness of BSCN reprogramming to regenerate RGCs.Therefore, the present application determines that microglia is a new type of reprogramming seed cell, and finds that four key genes are involved in RGCs regeneration to restore vision, which provides a new therapeutic drug and means for the treatment of glaucoma and related diseases.