Methods are provided for treatment of cancer in a subject's body by intraluminal delivery of oncolytic viruses through a balloon catheter or alternative mechanism inserted in a blood vessel or duct leading to a target site of the cancer tissue, or for somatic cell gene therapy of single defective gene-caused other diseases or disorders by similar intraluminal delivery of non-oncolytic viruses to a target site of affected tissue and cells of the disease or disorder, wherein during delivery of the oncolytic or non-oncolytic virus, the designated vessel or duct is selectively occluded at both ends of the target site by two spaced-apart inflated balloons of the catheter to block perfusion therethrough and allow control of the volume of virus delivered to the target site so as to increase concentration and pressure of the virus thereat sufficient to enable viral penetration of an endothelial barrier of the vessel or duct without compromise thereof and into diseased cells in the vicinity of the target site toward achieving a desired therapy.

The present subject matter provides, inter alia compositions, formulations, and methods for inhibiting, treating, and preventing small vessel diseases.

The present inventions relates to the use of an isolated nucleic acid molecule comprising a nucleotide sequence coding for a hyperpolarizing light-gated ion channel or pump gene from an archeon or for a light-active fragment of said gene, or the nucleotide sequence complementary to said nucleotide sequence, for treating or ameliorating blindness. The light-gated ion channel or pump gene can be a halorhodopsin gene.

The invention pertains to a lipid-based microbubble stably binding a plurality of nucleic acids, and a method of delivering the microbubble and nucleic acids to a specific target site using ultrasound. The delivered nucleic acids create transgenic cells (i.e., for example, a transgenic tumor cell), wherein the transgenic cell expresses the proteins encoded by the delivered nucleic acids. This technology provides a significant improvement for microbubble-drug delivery platforms as known microbubble do not efficiently bind nucleic acids. The improvements described herein include but are not limited to identifying proper lipid proportionality ratios and/or cationic surfactant layers that provide an optimum mechanical index compatible with ultrasonics. Microbubble perfusion and/or nucleic acid delivery may be performed by a combination of imaging and ultrasound/microbubble targeted delivery to simultaneously perform low power two-dimensional imaging and high power microbubble destruction. Such systems are useful in therapeutics and/or diagnostics. For example, the data disclosed herein shows proof of principle in conjunction with the delivery of therapeutic siRNA molecules to slow tumor growth.

The present invention relates to expression constructs and vectors for the treatment and/or prevention of diseases that are associated with a loss of NPC1 function, such as the lysosomal storage disorder Niemann-Pick type C (NPC) disease.

A therapeutic regimen useful for treatment of GM1 gangliosidosis comprising administration of a recombinant adeno-associated virus (rAAV) vector having an AAV capsid and a vector genome comprising a sequence encoding human β-galactosidase is provided. Also provided are compositions containing a rAAV vector and methods of treating GM1 gangliosidosis in patient comprising administration of a rAAV vector.

Despite the eye's immune-privileged status, a secondary loss of vision in some patients treated with AAV led the inventors to question the immunogenicity of AAV vectors after a subretinal injection. The inventors thus characterized anti-transgene and anti-capsid immune responses induced in the periphery after the subretinal AAV injection. Different doses of AAV8 encoding reporter proteins fused with the HY male antigen were injected at day 0 into the subretinal space of adult immunocompetent C57BL/6 female mice. Subretinal AAV injection induced a dose-dependent proinflammatory immune response to the transgene product, correlated with local transgene expression. In order to trigger a subretinal-associated immune inhibition (SRAII) mechanism, some mice were co-injected subretinally at day 0 with AAV and HY peptides. Interestingly, this subretinal co-injection of AAV8 with peptides of the transgene product modulated the anti-transgene T-cell immune response, even at high dose of vector (5.10.sup.10 vg). This immunodulation was also confirmed in a pathophysiological murine model of retinal degeneration. The inventors also demonstrated that injection of AAV8 in the subretinal space induces proinflammatory peripheral immune responses to the transgene and the capsid that could be counteracted y co-injection with transgene peptides. Accordingly, the object of the present invention is to provide methods for preventing induction of immune responses to the transgene product and the AAV capsid after ocular gene therapy.

The present invention provides, among other things, methods and compositions for treating primary ciliary dyskinesia (PCD) based on mRNA therapy. The compositions used in treatment of PCD comprise an mRNA comprising a dynein axonemal intermediate chain 1 (DNAI1) coding sequence and are administered at an effective dose and an administration interval such that at least one symptom or feature of PCD is reduced in intensity, severity, or frequency or has a delayed onset. mRNAs with optimized DNAI1 coding sequences are provided that can be administered without the need for modifying the nucleotides of the mRNA to achieve sustained in vivo function.

Methods and compositions for modifying the expression of endogenous genes or modifying the coding sequence of endogenous genes.

Provided is a pharmaceutical composition for treating a degenerative brain disease, including a glycine transporter as an active ingredient. A composition including, as an active ingredient, a glycine transporter protein, a fragment thereof or a nucleic acid molecule encoding the protein or the fragment thereof, a vector including the nucleic acid molecule, or a cell transformed with the vector including the nucleic acid molecule, according to an embodiment, not only can achieve excellent effect(s) of inhibiting amyloid-beta aggregation and/or degrading aggregated amyloid-beta, but also degrades tau protein (and/or inhibition of the aggregation thereof), inhibits the hyperphosphorylation of tau protein, and has excellent blood-brain barrier permeability, thus making it possible to successively act on brain tissues. Therefore, the composition can be effectively applied to the prevention and/or treatment of various degenerative brain diseases associated with amyloid-beta aggregation, tau protein aggregation, and/or hyperphosphorylated tau protein.