Nucleic acid vectors encoding light-gated cation-selective membrane channels, in particular channelrhodopsin-2 (Chop2), converted inner retinal neurons to photosensitive cells in photoreceptor-degenerated retina in an animal model. Such treatment restored visual perception and various aspects of vision. A method of restoring light sensitivity to a retina of a subject suffering from vision loss due to photoreceptor degeneration, as in retinitis pigmentosa or macular degeneration, is provided. The method comprises delivering to the subject by intravitreal or subretinal injection, the above nucleic acid vector which comprises an open reading frame encoding a rhodopsin, to which is operatively linked a promoter and transcriptional regulatory sequences, so that the nucleic acid is expressed in inner retinal neurons. These cells, normally light-insensitive, are converted to a light-sensitive state and transmit visual information to the brain, compensating for the loss, and leading to restoration of various visual capabilities.

The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells, in shorter times than previously and/or in whole blood or a component thereof. In some embodiments a lymphodepletion filter assembly is used before or after forming a reaction mixture where lymphocytes are contacted with recombinant retroviral particles in a closed system, to genetically modify the lymphocytes.

Provided are antigen-density sensing molecular circuits and methods of using the same. Aspects of such circuits will generally include an antigen-triggered switch component and a therapeutic component specific for the same antigen as the antigen-triggered switch component. The circuits will generally be configured such that expression of the therapeutic component is induced by the antigen-triggered switch component when the switch is activated by binding the antigen. Nucleic acids, expression constructs, vectors and the like encoding such circuits, and cells genetically modified to include an antigen-density sensing molecular circuit are also provided. Also provided are methods of making antigen-density sensing molecular circuits, methods of inducing expression of high affinity therapeutics specific to an antigen expressed by a target cell, methods of activating an immune response to a target cell, methods of treating a subject for a cancer expressing an antigen, and the like, where such methods involve antigen-density sensing molecular circuits.

A method and vectors for controlling blood glucose levels in a mammal are disclosed. In one embodiment, the method comprises the steps of: treating the hepatocyte cells of a patient with a first, second or third vector, wherein the first vector comprises a promoter enhancer, glucose inducible regulatory elements, a liver-specific promoter, a gene encoding human insulin with modified peptidase and an albumin 3′UTR and lacks an HGH intron, wherein the second vector comprises an HGH intron, glucose inducible regulatory elements, a liver-specific promoter, a gene encoding human insulin with modified peptidase site and an albumin 3′UTR and lacks a promoter enhancer, wherein the third vector comprises an HGH intron, glucose inducible regulatory elements, a liver-specific promoter, a gene encoding human insulin with modified peptidase site, an albumin 3′UTR and a promoter enhancer and observing the patient's insulin levels, wherein the patient's insulin levels are controlled.

The present invention relates to methods and compositions for treating, ameliorating or preventing a disease or disorder in a subject by introducing into cells of the subject a therapeutic gene switch construct that controls expression of one or more therapeutic products.

The present invention features modified human transcription factors capable of increasing utrophin expression, recombinant adeno-associated vectors for delivery of the modified human transcription factors, and methods of treating muscle diseases, including Duchenne's muscular dystrophy.

The disclosure herein relates to engineered biosensor-containing bacteria, which is bacteria that contain at least one biosensor circuit, and uses thereof. A biosensor circuit can comprise an essential gene of the bacteria operably linked to an inducible promoter. Additionally, the bacteria can be engineered to be deficient in the endogenous copy of the at least one essential gene.

An expression cassette including a gene of interest under the control of an inducible promoter, characterized in that said inducible promoter includes at least one CARE regulatory sequence (C/EBP-ATF responsive element) and a minimal promoter. Also, a vector and a host cell, as well as to a pharmaceutical composition including such a cassette, and to the use thereof for treating diseases by gene therapy.

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).

The present invention provides methods for modulating expression of endogenous cellular genes using recombinant zinc finger proteins.