168 results about "HIV receptor" patented technology

The present invention concerns methods and compositions for treatment of HIV infection in a subject, utilizing a DNL complex comprising at least one anti-HIV therapeutic agent, attached to an antibody, antibody fragment or PEG. In a preferred embodiment, the antibody or fragment binds to an antigen selected from gp120, gp41, CD4 and CCR5. In a more preferred embodiment the antibody is P4 / D10 or 2G12, although other anti-HIV antibodies are known and may be utilized. In a most preferred embodiment, the anti-HIV therapeutic agent is a fusion inhibitor, such as T20, T61, T651, T1249, T2635, CP32M or T-1444, although other anti-HIV therapeutic agents are known and may be utilized. The DNL complex may be administered alone or may be co-administered with one or more additional anti-HIV therapeutic agents.

The present invention provides an expression vector for preventing or inhibiting HIV entry, fusion or replication in mammalian cells. In particular, the invention provides a recombinant retroviral vector that encodes an inhibitor of a HIV co-receptor, such as CCR5 or CXCR4, and a protein that inhibits HIV fusion to target cells and / or HIV replication. Pharmaceutical compositions comprising such constructs and methods of use thereof to prevent or treat HIV infection in a patient are also disclosed.

The invention relates to the field of gene therapy, in particular relates to sgRNA (singleguide Ribonucleic Acid), as well as a lentiviral vector constructed by the same and application thereof and specifically relates to sgRNA with SIVmac1A11 lentivirus as a framework to express SpCas9 protein and gene specificity. The sgRNA is applied to treating human and simian AIDS (Acquired Immune Deficiency Syndrome). A nucleotide sequence of the sgRNA is shown as SEQ ID NO.1 to 2. According to the sgRNA disclosed by the invention, a current most efficient CRISPR / Cas9 gene editing tool is utilized, a designed CXCR4 / CCR5 gene sgRNA locus has gene knockout activity superior to other loci reported by existing research, and the sgRNA is applied to gene therapy of SIV infected rhesus monkeys for the first time. Compared with ZFN and TALEN, the sgRNA has the advantages of being convenient to operate, low in cost and the like.

A change in viral tropism occurs in many HIV positive individuals over time and can be indicated by a shift in coreceptor use from CCR5 to CXCR4. The shift in coreceptor use to CXCR4 has been shown to correlate with increased disease progression. In patients undergoing HAART, the predominant populations of virus can be shifted back to CCR5-mediated entry after the CXCR4-specific strains have emerged. The present invention relates to a diagnostic method to monitor coreceptor use in the treatment of human immunodeficiency virus (HIV) infection. The present invention further relates to a diagnostic method applied to HIV-positive individuals undergoing HAART to monitor the suppression of CXCR4 specific strains. The diagnostic methods can be used to assist in selecting antiretroviral therapy and to improve predictions of disease prognosis over time.

Compositions are provided that comprise antibody against coreceptors for human immunodeficiency virus such as CCR5 and CXCR4. In particular, monoclonal human antibodies against human CCR5 are provided that bind to CCR5 with high affinity and are capable of inhibiting HIV infection at low concentrations. The antibodies can be used as prophylactics or therapeutics to prevent and treat HIV infection, for screening drugs, and for diagnosing diseases or conditions associated with interactions with HIV coreceptors.

The present invention provides an expression vector for preventing or inhibiting HIV entry, fusion or replication in mammalian cells. In particular, the invention provides a recombinant retroviral vector that encodes an inhibitor of a HIV co-receptor, such as CCR5 or CXCR4, and a protein that inhibits HIV fusion to target cells and / or HIV replication. Pharmaceutical compositions comprising such constructs and methods of use thereof to prevent or treat HIV infection in a patient are also disclosed.

The present invention is based, at least in part, on the discovery of compositions and methods for the treatment and prevention of infectious diseases or disorders, e.g., HIV infection, AIDS, and AIDS-related diseases. In particular, the present invention pertains to methods of modulating cellular gene expression or protein activity, e.g., CCR5, gene expression or protein activity and / or gene expression or protein activity of a gene or sequence of an infectious agent, in order to treat or prevent infectious diseases or disorders, HIV infection, AIDS, or an AIDS-related disease or disorder. In one embodiment the combination of an RNA interfering agent targeting a cellular gene in combination with an RNA interfering agent targeting a gene or sequence of an infectious agent results in prolonged prevention of infection by an infectious agent The present invention is based on the identification of novel RNA interference agents, e.g., siRNA molecules, which target cellular genes, e.g., chemokine receptors, e.g., the CCR5 gene, and result in inhibition of target gene expression on target gene expressing cells, thereby inhibiting entry of infectious agents, e,g., HIV infection into target cells, prevention infection, and / or suppressing replication in established infection.

The present invention relates to compounds of Formula I: wherein variable substituents are defined herein, that modulate the activity of or bind to chemokine receptors such as CCR5. In some embodiments, the compounds of the invention are selective for CCR5. The compounds can be used, for example, to treat diseases associated with chemokine receptor expression or activity such as inflammatory diseases, immune diseases and viral infections.

The present invention provides a compound of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R<1>, R<2>, R<3>, R<9>, R<10>, A and B are as defined in the specification. The present invention also provides pharmaceutical compositions containing the compound of this invention, and methods of treatment using the compound of this invention. The invention also relates to the use of a combination of a compound of this invention and one or more antiviral or other agents useful in the treatment of Human Immunodeficiency Virus (HIV). The invention further relates to the use of a compound of this invention, alone or in combination with another agent, in the treatment of solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis.

In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector (FIG. 1A). Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle. In yet a further aspect, the invention provides methods for expression of a small RNA molecule within a cell, such as an siRNA capable of downregulating CCR5, wherein expression of the small RNA molecule is relatively non-cytotoxic to the cell. The invention also includes small RNA molecules, such as an siRNA capable of downregulating CCR5, that are relatively non-cytotoxic to cells.