Methods of treating cancer in Non-Responder Patients with an engineered NeoTCR Product are described herein.

The present disclosure provides methods and compositions for the treatment of diseases and genetic disorders linked to SLC6A1 loss and/or misfunction. The methods and compositions of the present disclosure comprise rAAV vectors and rAAV viral vectors comprising transgene nucleic acid molecules comprising nucleic acid sequences encoding for a GAT1 polypeptide.

Disclosed herein, in one aspect, is a method of reducing immunogenicity, comprising administering to a patient receiving or having received a biological therapeutic agent, an effective amount of B cell inhibitor that is non-depletional. Related compositions are also provided.

Provided herein are methods for enhancing gene therapy in an individual by administering an IRAK modulator (e.g., an IRAK-4 degrader) with the gene therapy to suppress innate immunity to the gene therapy. In some embodiments, the gene therapy uses an adeno-associated virus (AAV) vector, an adenovirus vector, a lentivirus vector, a Herpes simplex virus (HSV) vector or a lipid nanoparticle. Also provided herein are methods for selecting an individual for treatment with an IRAK modulator in combination with a gene therapy agent.

A method of using RNA interference (RNAi) for the transient, reversible and controlled opening of the tight junctions of the blood brain barrier and/or the blood retinal barrier. This method may be used in the treatment of many diseases and disorders which require the opening of the blood brain barrier and/or blood retinal barrier. Such methods generally involve the use of an RNAi-inducing agent, such as siRNA, miRNA, shRNA or an RNAi-inducing vector whose presence within a cell results in production of an siRNA or shRNA, targeting tight junction proteins to open the blood brain barrier and/or blood retinal barrier.

The present invention relates to an improved method of providing photoreceptor function to a cell, for example for use in the treatment of retinal degeneration. The present invention also relates to compositions and kits, in particular for use in such methods.

Lipid nanoparticles comprising CRISPR/Cas synergistic activation mediator system components together in the same lipid nanoparticle and methods of using such lipid nanoparticles to increase expression of target genes in vivo and ex vivo and to assess CRISPR/Cas synergistic activation mediator systems for the ability to increase expression of target genes in vivo and ex vivo are provided.

A localizable systemic gene therapy system is provided substantially increasing the transfection efficiency of the gene vectors into targeted tissue cells and substantially reducing the escape of the gene vectors from the targeted tissue volume, such as would waste the vectors, promote undesired immune reactions, and/or incur prohibitive costs for the required dose of gene-containing virus vectors. In this regard, the invention provides a means to simultaneously achieve local electroporation and gene-containing vector injection in a portion of a vascularized organ. It includes two double-balloon catheters that create contained volumes in parallel blood vessels for the introduction of vectors with reduced loss along with electrodes providing electroporation of the cells in the same location where the vectors are injected.

RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 g and 100 g. Thus the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 g and 100 g of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

Compositions and methods for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), particularly forms of the disease that are inherited in an autosomal dominant manner, by way of calsequestrin 2 (CASQ2) gene therapy can be used to treat CPVT caused by mutations in, for example, ryanodine receptor 2 and calmodulin, such as calmodulin 1 (CALM1) and CALM3. A variety of vectors are provided that can be used for the delivery of a CASQ2 transgene to a patient, such as a human patient suffering from autosomal dominant CPVT, including adeno-associated virus vectors, among others.