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.

The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.

The present disclosure provides antisense oligonucleotides, compositions, and methods that target ATP7B exon 6 or a flanking intron, thereby modulating splicing of ATP7B pre-mRNA to increase the level of ATP7B mRNA molecules having exon 6, e.g., to provide a therapy for Wilson disease. The present disclosure provides an antisense oligonucleotide including a nucleobase sequence at least 70% complementary to an ATP7B target sequence in exon 6, a 5′-flanking intron, a 3′-flanking intron, or a combination of exon 6 and the 5′-flanking or 3′-flanking intron.

The invention concerns KDM5A inhibitors for use in prevention or treatment of idiopathic inflammatory myopathies such as polymyositis, dermatomyositis, necrotizing autoimmune myopathy, and in particular sporadic inclusion body myositis, and diagnosis of these diseases based on KDM5A expression levels in muscle tissue. The invention further concerns pharmaceutical compositions comprising KDM5A inhibitors for use in prevention or treatment of idiopathic inflammatory myopathies such as polymyositis, dermatomyositis, necrotizing autoimmune myopathy, and in particular sporadic inclusion body myositis.

The disclosure relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the DNAJB 1-PRKAC A fusion gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of DNAJB 1-PRKAC A fusion.

The present disclosure features useful compositions and methods to treat trinucleotide repeat expansion disorders, e.g., in a subject in need thereof. In some aspects, the compositions and methods described herein are useful in the treatment of disorders associated with OGG1 activity.

The present invention includes a method of increasing, stimulating, inducing, promoting, enhancing or maintaining the genomic stability of a cell of a subject, the method comprising decreasing, reducing, inhibiting, suppressing, limiting or controlling loss of methylation of heterochromatin in the cell and/or modulating heterochromatin dysfunction in a cell of a subject, the method comprising activating, eliciting, stimulate ng, inducing, promoting, increasing or enhancing expression or activity in the cell of one or more DNA methyltransferase (DNMT).

The present disclosure provides compositions and methods for enhancing immunity (or immune response). The compositions and methods are particularly useful for potentiating immune response of a lymphoid cell. The compositions and methods are also applicable for treating cancer and other diseases.

Methods and compositions for producing fetal hemoglobin and treating a hemoglobinopathy or thalassemia are disclosed.

The present disclosure provides methods of treating subjects having psoriasis, and methods of identifying subjects having an increased risk of developing psoriasis.