344 results about "CXCR4" patented technology

The invention belongs to the field of pharmaceutical and biological engineering, and relates to a CRISPR/Cas9 recombinant lentiviral vector for human immunodeficiency virus gene therapy and a lentivirus of the CRISPR/Cas9 recombinant lentiviral vector. The recombinant lentiviral vector is prepared by carrying out enzyme digestion on a lentiviral vectorlentiCRISPR by BsmBI and connecting into a BsmBI cohesive end-containing CXCR4 specific target sequence to recombine; the obtained CRISPR/Cas9 recombinant lentiviral vector is capable of mutating gene sequences at four different loci of ahuman immunodeficiency virusco-receptor CXCR4 and themutatuin rate is high and up to 25-75%. The cells transformed by the recombinant lentiviral vector cannot be infected by the human immunodeficiency virus. Compared with theRNAi-Knockdown, ZFN and TALEN technologies, the method has higher efficiency of suppressing the human immunodeficiency virus replication; the system is rapid to construct, simple and low in cost, is capable of preventing the invasion of the human immunodeficiency virus and is suitable for human immunodeficiency virus gene therapy.

The invention relates to chimeric molecules comprising a virus coat sequence and a receptor sequence that can interact with each other to form a complex that is capable of binding a co-receptor. Such chimeric molecules therefore exhibit functional properties characteristic of a receptor-coat protein complex and are useful as agents that inhibit virus infection of cells due to occupancy of co-receptor present on the cell, for example. In particular aspects, the chimeric polypeptide includes an immunodeficiency virus envelope polypeptide, such as that of HIV, SIV, FIV, FeLV, FPV and herpes virus. Receptor sequences suitable for use in a chimeric polypeptide include, for example, CCR5 and CXCR4 sequences.

The current invention provides a method for mobilising endothelial progenitor cells (EPC) and/or mesenchymal stem cells (MSC) in a patient, wherein the method comprises the steps of (i) administering a vascular endothelial growth factor receptor (VEGFR) agonist to the patient; and (ii) administering an antagonist of CXCR4 to the patient. Also provided are uses of EPC and MSC harvested using the methods of the invention.

A method is provided for diagnosing and monitoring kidney disease or a predisposition to kidney disease, in a subject comprising detecting pVHL, VEGF-A, CXCR4, integrin β-1, PDGF-A, HIF1α and/or TGFβ in a sample from the subject. Screening methods for test agents for inhibiting kidney disease, and therapeutic applications are also described.

Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formula

Z-linker-Z′  (1)

or pharmaceutically acceptable salt thereof

wherein Z is of the formula

wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms, Z′ is of the formula

—Ar(Y)_j;

wherein Ar is an aromatic or heteroaromatic moiety, and each Y is independently a non-interfering substituent and j is 0-3; and “linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms.

The present invention relates to compounds that bind to chemokine receptors, and having the formula

wherein each A, X, Y, R¹, R² and R³ are substituents. The present invention also relates to methods of using such compounds, such as in treating HIV infection and inflammatory conditions such as rheumatoid arthritis. Furthermore, the present invention relates to methods to elevate progenitor and stem cell counts, as well as methods to elevate white blood cell counts, using such compounds.

The invention belongs to the field of genetic engineering, discloses a streptococcus thermophilus derived target sequence recognizable by a CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR associated 9) system and further discloses a sgRNA (single guide ribonucleic acid) and a coding DNA (deoxyribonucleic acid) molecule thereof. The target sequence is shown as n-20th of any one of SEQ ID NO:1-63, wherein n=1-5. A sequence of the sgRNA is 5'-recognition sequence- Cas9 protein recruitment sequence-3', and a DNA sequence corresponding to the recognition sequence is identical to the target sequence. The invention also discloses the CRISPR-Cas9 system, and the CRISPR-Cas9 system comprises Cas9 proteins and sgRNA and/or comprises carriers carrying a Cas9 protein coding sequence and a sgRNA coding sequence. The invention further discloses application of the CRISPR-Cas9 system to CXCR4 gene editing and preparation of medicines for treating HIV (human immunodeficiency virus) infection. CXCR4 gene editing can be realized to protect cells from HIV infection.

The present disclosure provides human monoclonal antibodies that bind specifically to CXCR4 with high affinity. This disclosure also provides a method for treating a subject afflicted with a CXCR4-expressing cancer, in particular a hematological malignancy such as multiple myeloma, acute myeloid leukemia, or non-Hodgkin's lymphoma, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an anti-CXCR4 antibody of the disclosure. The disclosure further provides a kit for treating a cancer in a subject comprising a dose of an anti-CXCR4 antibody and instructions for using the anti-CXCR4 antibody in the therapeutic methods of the disclosure.

Populations enriched for myogenic progenitors are obtained by selection on the basis of expression of specific cell surface markers. The muscle progenitor cells are characterized as being CD45⁻ and CD34⁺, and may further be characterized as lacking expression of Mac-1 (CD11b) and positive for expression of CXCR4 (CD184) and β1-integrin (CD29).

Compositions and methods of treating ocular disorders comprising CXCR4 inhibitory compositions.

Inhibition of CXCR4 can inhibit tumor growth and metastasis during certain therapeutic windows. Disclosed are novel methods for treating and preventing cancer in a subject related to administration of CXCR4 inhibitors during a therapeutic window following treatment with another anti-tumor therapy.

The invention provides compounds, pharmaceutical compositions and methods of use of certain compounds that are antagonists of the chemokine CXCR4 receptor for the treatment of proliferative conditions mediated by CXCR4 receptors. The compounds provided interfere with the binding of SDF1 to the receptor. These compounds are particularly useful for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis.

A compound represented by general formula (I):

a salt thereof, a solvate thereof, or a prodrug thereof wherein all symbols are as defined in the specification. The compound of the present invention has antagonistic activity against CXCR4 and is therefore useful as a preventive and/or therapeutic agent for CXCR4-mediated diseases, for example, inflammatory and immune diseases (for example, rheumatoid arthritis, arthritis, systemic erythematosus, retinopathy, macular degeneration, pulmonary fibrosis, transplanted organ rejection, etc.), allergic diseases, infections (for example, human immunodeficiency virus infection, acquired immunodeficiency syndrome, etc.), psychoneurotic diseases, cerebral diseases, cardiovascular disease, metabolic diseases, cancerous diseases (for example, cancer, cancer metastasis, etc.), or an agent for regeneration therapy.

The invention provides compounds, pharmaceutical compositions and methods of use of certain compounds that are antagonists of the chemokine CXCR4 receptor for the treatment of proliferative conditions mediated by CXCR4 receptors. The compounds provided interfere with the binding of SDF1 to the receptor. These compounds are particularly useful for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis.

An isolated mesenchymal stem cell, multipotent adult progenitor cell, or other stem cells is genetically modified to express at least one of CXCR4, SDF-1, or a variant thereof.

The invention discloses a gRNA, a knockout system and a kit for knocking out CXCR4 gene. A target site with high cutting efficiency is screened, the gRNA specifically targeting a target gene is designed and prepared, the CXCR4 gene can be effectively knocked out by CRISPR-Cas9 technology, HIV virus co-receptor CXCR4 on cell surface can be knocked out by CRISPR-nickase gene editing technology, theoff-target efficiency can be greatly reduced under the premise of effective CXCR4 gene knockout, the feasibility of clinical use is improved, and security risks can be reduced.