Abstract: Provided are methods and compositions for genome editing using a delivery vehicle with multiple payloads. In some embodiments the delivery vehicle includes a payload that includes (a) one or more sequence specific nucleases that cleave the cell's genome or one or more nucleic acids encoding same, (b) a first donor DNA, which includes a nucleotide sequence that is inserted into the cell's genome, where insertion of said nucleotide sequence produces, in the cell's genome at the site of insertion, a target sequence (e.g., an attP site) for a site-specific recombinase; (c) the site-specific recombinase (or a nucleic acid encoding same) (e.g., ?C31, ?C31 RDF, Cre, FLP), where the site-specific recombinase recognizes said target sequence; and (d) a second donor DNA, which includes a nucleotide sequence that is inserted into the cell's genome as a result of recognition of said target sequence by the site-specific recombinase.

Abstract: Provided are methods and compositions for the heterologous expression of a payload (e.g., DNA, RNA, protein) of interest in a target cell (e.g., cancer cell). In some cases payload delivery results in expression (e.g., by a cancer cell in vivo) of a secreted immune signal such as a cytokine, a plasma membrane-tethered affinity marker (thus resulting in an induced immune response), or a cytotoxic protein such as an apoptosis inducer (e.g., by a cancer cell in vivo). Payloads are delivered with a delivery vehicle and in some cases the delivery vehicle is a nanoparticle. In some cases a subject nanoparticle includes a targeting ligand for targeted delivery to a specific cell type/tissue type (e.g., a cancerous tissue/cell). In some embodiments, payload delivery is “personalized” in the sense that the delivery vehicle and/or payload can be designed based on patient-specific information.

Abstract: Provided are methods and compositions for delivering a nucleic acid, protein, and/or ribonucleoprotein payload to a cell. Also provided are delivery molecules that include a peptide targeting ligand conjugated to a protein or nucleic acid payload (e.g., an siRNA molecule), or conjugated to a charged polymer polypeptide domain (e.g., poly-arginine such as 9R or a poly-histidine such as 6H, and the like). The targeting ligand provides for (i) targeted binding to a cell surface protein, and (ii) engagement of a long endosomal recycling pathway. As such, when the targeting ligand engages the intended cell surface protein, the delivery molecule enters the cell (e.g., via endocytosis) but is preferentially directed away from the lysosomal degradation pathway.

Abstract: Provided are methods and compositions for delivering a nucleic acid, protein, and/or ribonucleoprotein payload to a cell. Also provided are delivery molecules that include a peptide targeting ligand conjugated to a protein or nucleic acid payload (e.g., an siRNA molecule), or conjugated to a charged polymer polypeptide domain (e.g., poly-arginine such as 9R or a poly-histidine such as 6H, and the like). The targeting ligand provides for (i) targeted binding to a cell surface protein, and (ii) engagement of a long endosomal recycling pathway. As such, when the targeting ligand engages the intended cell surface protein, the delivery molecule enters the cell (e.g., via endocytosis) but is preferentially directed away from the lysosomal degradation pathway.

Abstract: Provided are methods and compositions for genome editing using sticky ends. Subject methods include (a) generating a staggered cut at each of two locations in genomic DNA of a target cell, thus generating two genomic staggered ends; and (b) providing/introducing a linear double stranded donor DNA that has staggered ends (i.e., sticky ends) that match/correspond to the sticky ends of the genomic DNA such that the sticky ends of the donor DNA hybridize with the sticky ends of the genomic DNA and the donor DNA is inserted into the genome. In some cases, the staggered cuts are generated by introducing into a target cell one or more sequence specific nucleases (or one or more nucleic acids encoding the one or more sequence specific nucleases).

Abstract: An improved nanoparticle for transfecting cells is provided. The nanoparticle includes a core polyplex and a silica coating on the core polyplex and, optionally, a polymer attached to an outer surface of the silica coating, where the polyplex includes an anionic polymer, a cationic polymer, a cationic polypeptide, and a polynucleotide. Also provided is an improved method of modifying intracellular polynucleotides. The method includes contacting a cell with a nanoparticle that includes a core polyplex and a silica coating on the core polyplex and, optionally, a polymer attached to an outer surface of the silica coating, where the polyplex includes an anionic polymer, a cationic polymer, a cationic polypeptide, and a polynucleotide.

Abstract: Provided are methods and compositions for genome editing using a delivery vehicle with multiple payloads. In some embodiments the delivery vehicle includes a payload that includes (a) one or more sequence specific nucleases that cleave the cell's genome or one or more nucleic acids encoding same, (b) a first donor DNA, which includes a nucleotide sequence that is inserted into the cell's genome, where insertion of said nucleotide sequence produces, in the cell's genome at the site of insertion, a target sequence (e.g., an attP site) for a site-specific recombinase; (c) the site-specific recombinase (or a nucleic acid encoding same) (e.g., ?C31, ?C31 RDF, Cre, FLP), where the site-specific recombinase recognizes said target sequence; and (d) a second donor DNA, which includes a nucleotide sequence that is inserted into the cell's genome as a result of recognition of said target sequence by the site-specific recombinase.

Abstract: Provided are methods and compositions for nanoparticle delivery of payloads (e.g., nucleic acid and/or protein payloads) to cells. In some embodiments, a subject nanoparticle includes a core and a sheddable layer encapsulating the core, where the core includes (i) an anionic polymer composition; (ii) a cationic polymer composition; (iii) a cationic polypeptide composition; and (iv) a nucleic acid and/or protein payload; and where: (a) the anionic polymer composition includes polymers of D-isomers of an anionic amino acid and polymers of L-isomers of an anionic amino acid, and/or (b) the cationic polymer composition comprises polymers of D-isomers of a cationic amino acid and polymers of L-isomers of a cationic amino acid. In some cases, the polymers of D-isomers of an anionic and/or cationic amino acid are present at a ratio, relative to the polymers of L-isomers, in a range of from 10:1 to 1:10.

Abstract: An improved nanoparticle for transfecting cells is provided. The nanoparticle includes a core polyplex and a silica coating on the core polyplex and, optionally, a polymer attached to an outer surface of the silica coating, where the polyplex includes an anionic polymer, a cationic polymer, a cationic polypeptide, and a polynucleotide. Also provided is an improved method of modifying intracellular polynucleotides. The method includes contacting a cell with a nanoparticle that includes a core polyplex and a silica coating on the core polyplex and, optionally, a polymer attached to an outer surface of the silica coating, where the polyplex includes an anionic polymer, a cationic polymer, a cationic polypeptide, and a polynucleotide.

Abstract: Provided are methods and compositions for nanoparticle delivery of payloads (e.g., nucleic acid and/or protein payloads) to cells. In some embodiments, a subject nanoparticle includes a core and a sheddable layer encapsulating the core, where the core includes (i) an anionic polymer composition; (ii) a cationic polymer composition; (iii) a cationic polypeptide composition; and (iv) a nucleic acid and/or protein payload; and where: (a) the anionic polymer composition includes polymers of D-isomers of an anionic amino acid and polymers of L-isomers of an anionic amino acid, and/or (b) the cationic polymer composition comprises polymers of D-isomers of a cationic amino acid and polymers of L-isomers of a cationic amino acid. In some cases, the polymers of D-isomers of an anionic and/or cationic amino acid are present at a ratio, relative to the polymers of L-isomers, in a range of from 10:1 to 1:10.

Abstract: Provided are methods and compositions for delivering a nucleic acid, protein, and/or ribonucleoprotein payload to a cell. Also provided are delivery molecules that include a peptide targeting ligand conjugated to a protein or nucleic acid payload (e.g., an siRNA molecule), or conjugated to a charged polymer polypeptide domain (e.g., poly-arginine such as 9R or a poly-histidine such as 6H, and the like). The targeting ligand provides for (i) targeted binding to a cell surface protein, and (ii) engagement of a long endosomal recycling pathway. As such, when the targeting ligand engages the intended cell surface protein, the delivery molecule enters the cell (e.g., via endocytosis) but is preferentially directed away from the lysosomal degradation pathway.

Abstract: An improved nanoparticle for transfecting cells is provided. The nanoparticle includes a core polyplex and a silica coating on the core polyplex and, optionally, a polymer attached to an outer surface of the silica coating , where the polyplex includes an anionic polymer, a cationic polymer, a cationic polypeptide, and a polynucleotide. Also provided is an improved method of modifying intracellular polynucleotides. The method includes contacting a cell with a nanoparticle that includes a core polyplex and a silica coating on the core polyplex and, optionally, a polymer attached to an outer surface of the silica coating, where the polyplex includes an anionic polymer, a cationic polymer, a cationic polypeptide, and a polynucleotide.

Abstract: The present invention relates to methods for the prevention and/or treatment of cardiovascular and allergic diseases and disorders, methods for inhibiting the growth of, or reducing the volume of, a solid tumor, as well as methods for preventing progression to AIDS in an HIV-infected human, by administering a peptide derived from T cell receptors, or a derivative thereof The present invention also relates to peptides derived from T-cell receptors, and derivatives thereof, which are useful in such methods.

Abstract: An extract of the skin or peel of passion fruit is prepared. The extract has the effect of ameliorating the symptoms of inflammation disorders, including asthma and osteoarthritis, in mammals, including humans, when administered in an effective amount.

Abstract: An extract of passion fruit is prepared. The extract has the effect of lowering blood pressure and serum nitric oxide levels in mammals. The extract also provides a hepatoprotective effect, as well as antioxidant and anti-inflammatory effects in mammals. A novel compound was identified in the extract and given the name edulilic acid.

Abstract: A high load structural bearing primarily comprising a high strength elastomer and a housing with top closure plate. The housing is composed of sidewalls and is attached to a bottom base plate. The elastomeric pad has its top edge chamfered to produce a void that allows the pad to expand while being compressed without being squeezed into the gap between the sidewalls and the closure plate. The high load elastomer and surrounding housing are designed such that the elastomer is loaded in two phases in a controlled, predictable fashion. In the first phase the elastomer expands unrestrained on its lateral sides until it makes contact with the sidewalls. In the second phase the elastomer vertical compression increases and subsequently tensile stresses existing at the end of the first phase are mitigated to a predetermined level via lateral confinement from the housing sidewalls.

Abstract: A method and apparatus for accessing a safe deposit box stored in a vault. The safe deposit box includes a customer lock and a bank lock, each of which must be opened to access the box. Apparatus is provided to permanently maintain the bank lock in an open position and to enable a customer to enter the vault without requiring the assistance of a bank teller.

Abstract: A filtering system which is secured to a traditional air register. The filter uses a flange adapted to encircle the outlet of the traditional air register. Connected to the flange is an air filtering material which collects the dust and pollen at the air register, before the air enters the room. In one embodiment of the invention, an electro-static charge is used by the filtering material to assist in the collection of the dust and pollen. To assist the user in determining when the filter system should be replaced, the air flow pushes a flag; hence as the air flow decreases as the filter becomes clogged, the location of the flag notifies the user that the air filter system should be replaced. While a hook-and-loop fastener is sometimes used to secure the filter to the air register, the preferred embodiment uses a releasable adhesive.

Abstract: An aerial still camera including: a video camera; a device for elevating the video camera relative ground level; structure for suspending the video camera from the elevating device; first self-levelling structure for levelling the video camera in a first direction; second self-levelling structure for levelling the video camera in a second direction; first drive structure for rotating the video camera to control the image scanned by the video camera along a first axis; second drive structure for rotating the video camera to control the image scanned by the video camera along a second axis; a tether attached at one end to the elevating device for holding the elevating device and the video camera in the elevated position, the tether including electrical conductors; and an electrical control device attached at another end of the tether for controlling the first and second drive structure so as to control the image scanned by the video camera, the control structure further including a video display so to display t