Abstract: The present disclosure is directed to polypeptides, such as polypeptides comprising an alkaline phosphatase and a bone-targeting moiety. Also disclosed are expression vectors, such as lentiviral expression vectors, including a nucleotide sequence encoding a polypeptide. Also disclosed are methods of treating hypophosphatasia or treating, mitigating, or preventing one or more symptoms of hypophosphatasia by administering to a subject in need of treatment thereof the disclosed polypeptides or host cells transduced to express any of the disclosed polypeptides.

Abstract: CNS metastases are a major cause of cancer deaths with few therapeutic options for treatment. Monoclonal anti-body-based therapy is one of the most successful therapeutic strategies for cancer; however, its efficacy is limited against CNS metastases due to insufficient CNS delivery. Here, we show significantly improved antibody delivery to the CNS using novel timed-release nanocapsules that encapsulate individual antibodies within a crosslinked phosphorylcholine polymer and gradually release cargo through hydrolysable crosslinkers. A single course of rituximab (RTX) nanocapsule treatment elevates RTX levels in the CNS by nearly 10-fold compared to native RTX. We improved control of CNS metastases in a murine xenograft model of non-Hodgkin lymphoma; moreover, using a xenograft humanized BLT mouse model, lymphomas were eliminated with a single course of RTX nanocapsule treatment. This approach is useful for treatment of cancers with CNS metastases and is generalizable for delivery of any antibody to the CNS.

Abstract: 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.

Abstract: Novel siRNA and shRNA nanocapsules and delivery methods are disclosed herein. These siRNA and shRNA nanocapsules and delivery methods are highly robust and effective. This invention provides a platform for RNAi delivery with low toxicity and long intracellular half-life for practical therapeutic applications.

Abstract: Novel siRNA and shRNA nanocapsules and delivery methods are disclosed herein. These siRNA and shRNA nanocapsules and delivery methods are highly robust and effective. This invention provides a platform for RNAi delivery with low toxicity and long intracellular half-life for practical therapeutic applications.

Abstract: The invention provides novel methods, materials and systems that can be used to generate viral vectors having altered tissue and cell targeting abilities. In illustrative embodiments of the invention, the specificity of lentiviral vectors was modulated by a thin polymer shell that synthesized and coupled to the viral envelope in situ. The polymer shell can confers such vectors with new targeting ability via agents such as cyclic RGD (cRGD) peptides that are coupled to the polymer shell. These polymer encapsulated viral vectors exhibit a number of highly desirable characteristics including a higher thermal stability, resistance to serum inactivation in vivo, and an ability to infect dividing and non-dividing cells with high efficiencies.

Abstract: The invention provides novel methods, materials and systems that can be used to generate viral vectors having altered tissue and cell targeting abilities. In illustrative embodiments of the invention, the specificity of lentiviral vectors was modulated by a thin polymer shell that synthesized and coupled to the viral envelope in situ. The polymer shell can confers such vectors with new targeting ability via agents such as cyclic RGD (cRGD) peptides that are coupled to the polymer shell. These polymer encapsulated viral vectors exhibit a number of highly desirable characteristics including a higher thermal stability, resistance to serum inactivation in vivo, and an ability to infect dividing and non-dividing cells with high efficiencies.

Abstract: 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.

Abstract: 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.

Abstract: Novel siRNA and shRNA nanocapsules and delivery methods are disclosed herein. These siRNA and shRNA nanocapsules and delivery methods are highly robust and effective. This invention provides a platform for RNAi delivery with low toxicity and long intracellular half-life for practical therapeutic applications.

Abstract: Novel siRNA and shRNA nanocapsules and delivery methods are disclosed herein. These siRNA and shRNA nanocapsules and delivery methods are highly robust and effective. This invention provides a platform for RNAi delivery with low toxicity and long intracellular half-life for practical therapeutic applications.

Abstract: 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.

Abstract: 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.

Abstract: The invention provides novel methods, materials and systems that can be used to generate viral vectors having altered tissue and cell targeting abilities. In illustrative embodiments of the invention, the specificity of lentiviral vectors was modulated by a thin polymer shell that synthesized and coupled to the viral envelope in situ. The polymer shell can confers such vectors with new targeting ability via agents such as cyclic RGD (cRGD) peptides that are coupled to the polymer shell. These polymer encapsulated viral vectors exhibit a number of highly desirable characteristics including a higher thermal stability, resistance to serum inactivation in vivo, and an ability to infect dividing and non-dividing cells with high efficiencies.

Abstract: The present invention provides targeted lentiviral vectors that are psuedotyped with mutated Sindbis envelopes. For example, mutations in the Sindbis E2 protein are used to alter viral titer, specificity, specificity index, tropism, and susceptibility to host immune response. Typically, one or more of the E1, E2, or E3 proteins can be mutated at one or more amino acid positions. The psuedotyped, targeted lentiviral vectors of the invention are used to transduce heterologous genes into a cell and can be used for in vivo and ex vivo therapeutic applications, as well as for diagnostic and research tool applications.

Abstract: 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.

Abstract: 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.

Abstract: Novel siRNA and shRNA nanocapsules and delivery methods are disclosed herein. These siRNA and shRNA nanocapsules and delivery methods are highly robust and effective. This invention provides a platform for RNAi delivery with low toxicity and long intracellular half-life for practical therapeutic applications.

Abstract: The present invention relates to retroviral vectors, particularly lentiviral vectors, pseudotyped with Sindbis envelope and targeted to specific cell types via a targeting moiety linked to the envelope.

Abstract: 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.