The present disclosure provides methods of promoting a persistent effector function of immune cells, comprising modifying the cells to overexpress c-Jun and reduced levels of a NR4A gene and/or protein. Also provided are modified cells, e.g., immune cell, which have been modified to overexpress c-Jun and express reduced levels of NR4A gene and/or protein. Overexpressing c-Jun and simultaneously reducing expression levels of a NR4A gene and/or protein leads to exhaustion/dysfunction resistant cells, which are apoptosis resistant and also immune checkpoint resistant, and also to the maintenance of anti-tumor function in tumor microenvironments.

Methods for manufacturing genetically engineered T cells expressing a chimeric antigen receptor (CAR), such as a CAR that binds human CD19, BCMA, or CD70, and having multiple additional gene edits, for example, a disrupted Regnase-1 gene, a disrupted TGFBRII gene, a disrupted TRAC gene, a disrupted β2M gene, or a combination thereof, using CRISPR/Cas gene editing systems.

Novel NTRK1 fusion molecules, detection reagents, and uses and kits for evaluating, identifying, assessing and/or treating a subject having a cancer are disclosed.

Oligonucleotides are provided herein that inhibit NR1H3 expression. Also provided are compositions including the same and uses thereof, particularly uses relating to treating diseases, disorders and/or conditions associated with NR1H3 expression.

The invention relates to RNA editing oligonucleotides (EONs) that can bring about specific editing of a target nucleotide (adenosine) in a target RNA molecule in a eukaryotic cell, wherein said oligonucleotide is for use in the treatment of Stargardt disease, and more preferably for the deamination of target adenosines present in the ABCA4 pre-mRNA or ABCA4 mRNA.

Embodiments of the disclosure encompass methods and compositions for producing engineered mesenchymal stem/stromal cells (MSCs). The disclosure concerns large-scale processes for producing MSCs that are engineered to have disruption of expression of one or more genes using CRISPR and also express at least one heterologous antigen receptor. Specific embodiments include particular parameters for the process.

Provided are methods, compositions, and cells for use in adoptive cell therapy for the treatment of cancer. The methods involve administering an effective amount of cells to a subject, wherein the cells are modified ex vivo to suppress endogenous Zbtb20 expression and/or activity within the modified cells. The cells may comprise a dominant negative Zbtb20 capable of suppressing endogenous Zbtb20 activity, at least one shRNA capable of suppressing endogenous Zbtb20 expression, or at least one sgRNA capable of suppressing endogenous Zbtb20 expression. The cells may further comprise an exogenous TCR and/or CAR suitable for treating cancer. The method can further involve administering one or more additional cancer therapies, such as cells which express at least one exogenous TCR and/or CAR suitable for treating cancer. The method can provide various advantages, such as a reduction and/or elimination of an amount of cancer cells in the subject.

The present invention relates to methods of treating or ameliorating seizures relating to disruptions in Ubiquitin Protein Ligase E3A (UBE3A) gene. More particularly, the invention relates to the use of BK channel antagonists for the prophylaxis or treatment of seizures in a subject with Angelman syndrome or related autism spectrum disorder (ASD). In some embodiments, BK channel antagonist is Paxilline, iberiotoxin (IBTX) or GAL-021.

Methods and systems to reduce neurotoxicity associated with the treatment of CD19.sup.+ B-cell hyperproliferative disorders are disclosed. Neurotoxicity is reduced by the use of agents that protect CD19.sup.+ neurovascular pericytes and/or CD19.sup.+ vSMCs from attack by CD19-targeted therapy, and by modification of CD19-targeted therapy to avoid CD19.sup.+ pericytes and/or CD19.sup.+ vSMCs.

Provided is a host factor specific for hepatitis B virus (HBV) infection. The specific host factor CREBH can remarkably enhance HBV infection. The specific host factor can, on the one hand, enhance entry of HBV, and on the other hand, enhance transcription of HBV to some extent. In the CREBH regulatory pathway there is a specific host factor SCARF2. During HBV infection, an N-terminus EGF-like domain of SCARF2 plays a crucial role in the infection and entry of HBV. The two correlated specific host factors provide a new target for inhibiting HBV infection.