This invention relates to recombinant viral vectors, preferably retroviral (RV), lentiviral (LV) or adeno-associated viral (AAV) vectors, compositions thereof, the use of the recombinant viral vectors or the compositions thereof, kits of parts comprising said recombinant viral vectors or compositions thereof and a catalytically active Cas9 or Cpf1 protein, methods for modifying the genome of a cell, and the cells obtainable by such methods.

Provided are a viral vector for treating autoimmune disease and diabetes and a construction method and an application thereof. The viral vector is a lentiviral expression plasmid or an adeno-associated viral expression plasmid cloned with mfat-1 gene, and the mfat-1 gene is as shown in SEQ ID NO: 1.

CAR cells targeting FLT3 antigens in combination with a secreted anti-PD-1 and anti-PD-L1 antibodies or anti-PD-1-anti-PD-L1 bispecific antibodies are described as a new method of cancer treatment. It is proposed that these combination therapies are safe and effective in patients and can be used to treat human tumors and cancer.

Disclosed herein are recombinant CMV vectors which may comprise a heterologous antigen that can repeatedly infect an organism while inducing a CD8+ T cell response to immunodominant epitopes of the heterologous antigen. The CMV vector may comprise a deleterious mutation in the US11 glycoprotein or a homolog thereof.

Disclosed herein are methods of treatment for an intraocular pressure (IOP)-associated condition in a subject, that include administering to the subject an effective amount of a tissue plasminogen activator (tPA) therapeutic agent. In one embodiment, the IOP-associated condition is glaucoma. The administration of a tPA therapeutic agent can be an extended administration intended to cause a reduction in IOP in the subject for a period of at least one day to a year or more, relative to IOP levels in the subject prior to administration of the tPA therapeutic agent. The tPA therapeutic agent can be, for example, tPA, a tPA derivative, a small molecule direct or indirect tPA agonist, or a gene therapy vector.

Persistence of HIV in anatomic sanctuary sites such as the brain prevents viral eradication. Although combination antiretroviral therapy (cART) inhibits viral replication to undetectable level by standard clinical assay, it does not selectively eliminate virus reservoirs. To target HIV reservoirs, the present inventor developed an HIV Rev-dependent lentiviral vector carrying a series of therapeutic genes, such as diphtheria toxin, anthrolysin O from Bacillus anthracis, human TRAF6, or the herpes simplex 1 virus thymidine kinase gene (HSV-tk). The present disclosure provides the Rev-dependent vectors for targeting viral reservoir in a SIV/rhesus macaque model. SIV-infected rhesus macaques were first treated with cART for over 6 months starting 12 weeks post infection, followed by injections with viral particles assembled from a SIV Rev-dependent vector carrying HSV-tk. Following particle injection, animals were further treated briefly (two weeks) with ganciclovir (GCV), which induces the killing of SIV+, HSV-tk expressing cells. cART was terminated following the GCV treatment, and there was observed a partial control of viral rebound over a period of 4 months after cART cessation. The animal was further treated with additional Rev-dependent vector particles, and viral load was diminished to the undetectable level for over 1 year in the absence of any treatment. These results suggest that the Rev-dependent vector, with or without a functional gene, has the potential to diminish viral reservoirs in vivo and can offer a cure of functional cure of HIV/SIV infection.

The present invention provides a method for producing microvesicles comprising a transgene product and/or a lentiviral RNA comprising a transgene, comprising the steps of: culturing a cell into which the transgene has been introduced using a lentiviral vector in vitro to extracellularly release microvesicles comprising the transgene product and/or the lentiviral RNA comprising the transgene, wherein said lentiviral vector is deficient in at least one structural protein gene and comprises the transgene under control of a telomerase reverse transcriptase (TERT) gene promoter in a lentiviral genome sequence, and collecting the microvesicles released; and a microvesicle obtained according to this method and its use.

Persistence of HIV in anatomic sanctuary sites such as the brain prevents viral eradication. Although combination antiretroviral therapy (cART) inhibits viral replication to undetectable level by standard clinical assay, it does not selectively eliminate virus reservoirs. To target HIV reservoirs, the present inventor developed an HIV Rev-dependent lentiviral vector carrying a series of therapeutic genes, such as diphtheria toxin, anthrolysin O from Bacillus anthracis, human TRAF6, or the herpes simplex 1 virus thymidine kinase gene (HSV-tk). The present disclosure provides the Rev-dependent vectors for targeting viral reservoir in a SIV/rhesus macaque model. SIV-infected rhesus macaques were first treated with cART for over 6 months starting 12 weeks post infection, followed by injections with viral particles assembled from a SIV Rev-dependent vector carrying HSV-tk. Following particle injection, animals were further treated briefly (two weeks) with ganciclovir (GCV), which induces the killing of SIV+, HSV-tk expressing cells. cART was terminated following the GCV treatment, and there was observed a partial control of viral rebound over a period of 4 months after cART cessation. The animal was further treated with additional Rev-dependent vector particles, and viral load was diminished to the undetectable level for over 1 year in the absence of any treatment. These results suggest that the Rev-dependent vector, with or without a functional gene, has the potential to diminish viral reservoirs in vivo and can offer a cure of functional cure of HIV/SIV infection.

Disclosed herein are recombinant CMV vectors which may comprise a heterologous antigen that can repeatedly infect an organism while inducing a CD8+ T cell response to immunodominant epitopes of the heterologous antigen. The CMV vector may comprise a deleterious mutation in the US11 glycoprotein or a homolog thereof.

Disclosed herein are methods of treatment for an intraocular pressure (IOP)-associated condition in a subject, that include administering to the subject an effective amount of a tissue plasminogen activator (tPA) therapeutic agent. In one embodiment, the IOP-associated condition is glaucoma. The administration of a tPA therapeutic agent can be an extended administration intended to cause a reduction in IOP in the subject for a period of at least one day to a year or more, relative to IOP levels in the subject prior to administration of the tPA therapeutic agent. The tPA therapeutic agent can be, for example, tPA, a tPA derivative, a small molecule direct or indirect tPA agonist, or a gene therapy vector.