Compositions and methods for treating neurofibromatic disorders are provided herein, such as expressing Merlin protein or a functional fragment thereof from a viral vector.

The present disclosure provides modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in an endogenous gene locus encoding DNMT3A. Compositions and methods of treatment are also provided.

Provided herein are methods and compositions for plakophilin-2 gene therapy for treating heart diseases such as arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic cardiomyopathy (ACM).

The present invention provides gene therapies for the treatment of Friedreich's ataxia. Specifically, the present invention provides a nucleic acid, cloning vector and transfer vector for the production of an adeno-associated virus (AAV) vector. The nucleic acid comprises (i) a nucleic acid sequence encoding frataxin, (ii) a phospho-glycerate-kinase (PGK) promoter, and (iii) a woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). The present invention also provides a pharmaceutical composition which comprises the AAV vector or nucleic acid. Also, the AAV vector, nucleic acid or pharmaceutical composition can be used as a medicament, specifically as a medicament for the treatment of Friedreich's ataxia.

The present disclosure provides nucleic acid molecules comprising a first inverted terminal repeat (ITR), a second ITR, and a genetic cassette encoding a target sequence. In some embodiments, the first ITR and/or the second ITR is an ITR of human bocavirus. Also disclosed are methods of using the nucleic acid molecules in gene therapy applications.

Disclosed are compositions and methods for treating neurological diseases, disorders, and injuries in a subject in need thereof. Particularly disclosed are compositions and methods for treating neurological diseases, disorders, and injuries that are associated with upper motor neurons in a subject in need thereof in which methods expression of ubiquitin carboxyl hydrolase ligase 1 (UCHL1) is modulated in the subject, for example, via gene therapy being administered to the subject in order to express UCHL1 in upper motor neurons of the subject. Also disclosed are expression vectors comprising the UCHL1 promoter operably linked to a nucleic acid encoding a therapeutic gene product.

The present disclosure provides codon optimized Factor VIII sequences, vectors, and host cells comprising codon optimized Factor VIII sequences, polypeptides encoded by codon optimized Factor VIII sequences, and methods of producing such polypeptides.

The present invention contemplates mRNA, episomal and retroviral genomic gene therapy based short-term, intermediate or long-term vaccine, immunization, protection or therapy—that can also be administered as a retroviral genomic gene therapy—method to provide mucosal and hematological protection to humans to protect against pandemic and non-pandemic viruses, bacterial infections, fungi, allergens or the cause of allergic reactions, systemic pathological conditions, cancer and anti-biowarfare agents (e.g. natural and unnatural viruses and toxins) where mucosal immunity and potentially hematological immunity is achieved through mRNA, episomal or genomic expression of dimeric immunoglobulin A1 (dIgA1) and dimeric immunoglobulin A2 (dIgA2). The present invention provides methods, immunoglobulin compositions and vector constructs to express potent immunoglobulins that are derived from human blood of a human currently infected with, affected by, exposed to or recovered from any of a wide range of allergens or the cause of allergic reactions, pathogens (including, viruses, virus mutants, bacterial infections and fungi) and systemic pathological ailments (including cancer and other disorders), developed from phage display technology or mice or other animals with a humanized immune systems, transgenic mice or chimeric antibodies a fusion of non-human vetebrates (e.g. mouse or rabbit) and human. The immunoglobulin compositions include the heavy chain variable, diversity and joining (VDJ or Variable Heavy Region genes) segment immunoglobulin DNA and/or polypeptide sequence from humans identified to have developed high affinity immunoglobulins against the antigen, protein or proteins of interest and either to use the exact immunoglobulin heavy chain and light chain polypeptide sequences identified from the memory B-cell that produced them or to modify or engineer some of the immunoglobulin heavy chain and light chain constant domains to reduce, change or modulate effector functions. Although, ideally there are no changes made to the immunoglobulins light and heavy chains as identified from the memory B-cell that produced them. Modification may occur at the Hinge region, Constant Heavy 2 (C.sub.H2) domain and Constant Heavy 3 (C.sub.H3) domain for the immunoglobulin heavy chain polypeptide with optional modification or change of Constant Heavy 1 (C.sub.H1), optional modification or change constant light (C.sub.L) chain domain. The resulting antibodies can either be used as a monoclonal or antibody cocktail of (Immunoglobulin Class G subclass1) IgG1, IgG2, IgG3 and other subclasses, IgA1 monomer and IgA2 monomer and dimeric IgA1 (dIgA1) and dimeric IgA2 (dIgA2) immu

The present invention provides a lentiviral vector genome comprising at least one modified viral cis-acting sequence, wherein at least one internal open reading frame (ORF) in the viral cis-acting sequence is disrupted.

The invention described herein provides a recombinant DNA viral particle comprising a protein shell encapsulating an RNA vector genome, as well as related compositions and uses thereof.