Compositions and methods for Cas-based ex vivo and in vivo gene therapy applications are provided.

Disclosed herein are systems and methods for the treatment of NF1 in a subject. The CRISPR/Cas-based genome editing systems may include a polynucleotide sequence encoding a guide RNA (gRNA) targeting a fragment of a mutant NF1 gene, a polynucleotide sequence encoding a Cas protein or a fusion protein comprising the Cas protein, and a polynucleotide sequence encoding a donor sequence comprising a fragment of a wild-type NF1 gene.

The present invention provides methods compositions and methods of preparing autologous (or allogeneic) B cells that secrete a monoclonal of interest useful in immunotherapy or B cells with an altered function.

An isolated recombinant parvovirus vector comprising a synthetic enhancer comprising plurality of enhancer sequences operably linked to a promoter, and methods of using the vector, are provided.

Provided herein are isolated DNA vectors comprising a heterologous gene, wherein the DNA vector is devoid of bacterial plasmid DNA and/or bacterial signatures, which can abrogate persistence in vivo. The invention also features pharmaceutical compositions (non-immunogenic pharmaceutical compositions) including the DNA vectors of the invention, which can be used for induction of long-term, episomal expression of a heterologous gene in a subject. The invention involves methods of treating a subject by administering the DNA vectors of the invention, including methods of treating disorders associated with a defect in a target gene.

The present invention relates to vectors and compositions for the treatment of glycogen storage disease III.

The present invention relates to methods and compositions for inhibiting metastatic spread of cancer and/or inhibiting progression of pre-existing metastatic disease in a subject using L1CAM inhibition.

A transcriptomic analysis of genes consistently upregulated in high producer clones were each evaluated for their ability to increase the production of a protein of interest. The products of these genes (metabolism influencing products (MIP)), such as actin, Erp27, Erp57, Foxa1, PPAR, Ca3, and Tagap, could be sub-categorized into different functional categories such as signaling, protein folding, cytoskeleton organization and cell survival.

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.

Provided herein are methods of treating or reducing the likelihood of a virus infection, such as a coronavirus infection, by delivering to a subject in need a Chromosome 19 Open Reading Frame 66 (C19orf66) or a regulatory factor that increases expression of the gene encoding C19ord66 in a cell in a subject. The C19orf66 or regulatory factor may be delivered as a polynucleotide (e.g. mRNA or DNA) or as a protein, and may be contained in a vehicle for delivery, such as a viral or non-viral vector. Also provided are polynucleotides, proteins, and vehicles (e.g. viral and non-viral vector) and composition thereof, including for use in the methods.