316 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, 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.

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 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 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.

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 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 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.

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 belongs to the technical field of biological medicine, and particularly relates to application of GLUT5 serving as a colorectal cancer biomarker in development of an in-vitro detection kit, a prognosis model and an inhibitor. The GLUT5 is highly expressed in colorectal cancer tumor-related fibroblasts (CAFs), the expression level of the GLUT5 is remarkably related to poor prognosis of a patient, and the GLUT5 can be used as a molecular basis for auxiliary diagnosis and an independent prognosis factor. In mechanism, the GLUT5 promotes tumor progression by mediating fructose metabolism reprogramming of the CAFs. A full-chain solution from early diagnosis and precise prognosis to targeted therapy is provided for colorectal cancer, and the clinical transformation value is remarkable.

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.

The present invention discloses the application of the PPP1R3B gene in the preparation of atherosclerotic detection reagents or therapeutic drugs. The present invention for the first time discovers that the PPP1R3B gene is a reliable target for the diagnosis and treatment of atherosclerosis. By exogenous up-regulation of the expression of PPP1R3B, inducing the polarization of M2-type MΦ macrophages, it can alleviate the plaque inflammatory microenvironment, promote glycolipid metabolic reprogramming, support the energy load required by cells, delay the progression of atherosclerotic plaques, improve the quality of life of cardiovascular disease patients, reduce the incidence of cardiovascular and cerebrovascular events, and can be applied to the preparation of atherosclerotic diagnostic reagents and therapeutic 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.

Systems, methods and composition for targeting polynucleotides are detailed herein. In particular, engineered DNA-targeting systems comprising novel Fanzor polypeptides and a reprogrammable targeting nucleic acid component and methods and application of use are provided.