The invention provides improved gene therapy vectors, compositions, and methods.

A method of therapeutic treatment by genome engineering in a subject in need thereof, which includes administering to the subject a ribonucleic acid (RNA) molecule including, from 5 to 3 an RNA Booster sequence that includes or is the following ribonucleic acid sequence: mmsknkkkm, wherein: m indicates an adenine (a) or cytosine (c); s indicates a guanine (g) or a cytosine (c); k indicates a guanine (g) or a uracyl (u); n indicates any nucleotide; and a sequence of interest encoding at least one genome editor.

Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

The present disclosure provides compositions and methods for the generation of an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. Generally, the composition and methods of the disclosure comprise three steps: a design process comprising one or more in silico bioinformatics steps to select and generate a library of potential antigens for use in the immunogenic composition; a formulation process, comprising in vitro testing of potential antigens, using various biochemical assays, and further combining two or more antigens to generate one or more immunogenic compositions; and an administering step, whereby the immunogenic composition is administered to a host animal, immune cell, subject or patient. Further steps may also be included, such as the isolation and production of antibodies raised by host immune response to the immunogenic composition.

The present invention provides a method of treating an intracellular infection in a subject wherein the method comprising administering to the subject an IAP antagonist. In certain embodiments the IAP antagonist is a Smac mimetic.

The present invention relates to a cell membrane penetrating peptide and an intracellular delivery carrier including the same. The intracellular delivery carrier of the present invention has an advantage of efficiently transferring substances into cells even at a low concentration thereof compared with the existing cell membrane penetrating peptide derived from the virus.

Provided herein are recombinant nucleic acid sequences derived from the C-terminal domain of the HIV-1 gp41 protein, and more specifically compositions and methods for using these epitopes to develop vaccine protection against HIV. Also provided here are monoclonal antibodies that specifically bind to these recombinant nucleic acid sequences derived from the C-terminal domain of the HIV-1 gp41 protein.

Peptidic positive allosteric modulators of TRPV1 are provided. Methods for the design of TPRV1 allosteric modulators are also described, as well as methods for the treatment of conditions such as pain, pruritus, and cancer.

Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

Stimulation of target cells using light, e.g., in vivo or in vitro, is implemented using a variety of methods and devices. One example involves a vector for delivering a light-activated NpHR-based molecule comprising a nucleic acid sequence that codes for light-activated NpHR-based molecule and a promoter. Either a high expression of the molecule manifests a toxicity level that is less than about 75%, or the light-activated NpHR-based proteins are expressed using at least two NpHR-based molecular variants. Each of the variants characterized in being useful for expressing a light-activated NpHR-based molecule that responds to light by producing an inhibitory current to dissuade depolarization of the neuron. Other aspects and embodiments are directed to systems, methods, kits, compositions of matter and molecules for ion pumps or for controlling inhibitory currents in a cell (e.g., in in vivo and in vitro environments).