The present invention relates to a polynucleotide comprising a Complement Factor I (CFI) nucleotide sequence encoding a CFI polypeptide or a fragment thereof. The invention further relates to a viral particle comprising a recombinant genome comprising the polynucleotide of the invention, and a composition comprising the polynucleotide or viral particle of the invention. The invention also relates to methods of using, and uses of, the polynucleotide, viral particle and/or composition of the invention. The invention also relates to methods of using, and uses of, a polynucleotide comprising a CFI nucleotide sequence, a viral particle comprising a recombinant genome comprising the polynucleotide, or a composition comprising the polynucleotide or viral particle.

Compositions and methods for the treatment of muscular dystrophies are provided.

Provided are improved compositions and methods for achieving gene therapy in hematopoietic cells and hematopoietic precursor cells, including erythrocytes, erythroid progenitors, and embryonic stem cells. Also provided are improved gene therapy methods for treating hematopoietic-related disorders. Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.

Described herein is a method for treating Alzheimer's disease (AD) by selective silencing of the amyloid precursor protein (APP) using Cas9 nuclease gene editing. Methods of making and using genetic constructs comprising a Cas9 nuclease and a sequence encoding guide RNA (gRNA) specific to APP capable of truncating the C-terminus of APP, as well as compositions comprising these constructs, are provided.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of signal-sensor polynucleotides, primary transcripts and mmRNA molecules.

The present invention relates in part to nucleic acids, including nucleic acids encoding proteins, therapeutics and cosmetics comprising nucleic acids, methods for delivering nucleic acids to cells, tissues, organs, and patients, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, therapeutics, and cosmetics produced using these methods, kits, and devices.

An expression vector containing appropriate mitochondrion-targeting sequences (MTS) and appropriate 3′UTR sequences provides efficient and stable delivery of a mRNA encoding a protein (CDS) to the mitochondrion of a mammalian cell. The MTS and 3′UTR sequences guide the CDS mRNA from the nuclear compartment of the cell to mitochondrion-bound polysomes, where the CDS is translated. This provides an efficient translocation of a mature functional protein into the mitochondria. A method of targeting mRNA expressed in the nuclear compartment of a mammalian cell to the mitochondrion is also provided. The vector and methods can be used to treat defects in mitochondrial function.

The present invention relates to a gene therapy vector which is useful in the treatment or prevention of hypertrophic cardiomyopathy in a subject in need thereof. The gene therapy vector of the invention comprises a nucleic acid sequence encoding a cardiac sarcomeric protein and a cardiomyocyte-specific promoter which is operably linked to said nucleic acid sequence. The invention furthermore relates to a cell which comprises the gene therapy vector. Pharmaceutical compositions which comprise the gene therapy vector and/or a cell comprising said vector are also provided. In another aspect, the invention relates to a method for treating or preventing hypertrophic cardiomyopathy in a subject by introducing the gene therapy vector of the invention into a subject in need of treatment.

Provided nucleic acid-based expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, within a target cell, including a target cell that is associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell. Also provided are formulations and systems, including fusogenic lipid nanoparticle (LNP) formulations and systems, for the delivery of nucleic acid-based expression constructs as well as methods for making and using such nucleic acid-based expression constructs, formulations, and systems for reducing, preventing, and/or eliminating the growth and/or survival of a cell, such as a senescent cell and/or a cancer cell, which is associated with aging, disease, or other condition as well as methods for the treatment of aging, disease, or other conditions by the in vivo administration of a formulation, such as a fusogenic LPN formulation, comprising an expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, in a target cell that is associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell.

There is provided a vector for treating retinal degeneration associated with Bardet-Biedl Syndrome (BBS), wherein the vector comprises a promoter operably linked to a BBS1 gene, wherein the promoter is selected from a rhodopsin kinase (RK) promoter, a cytomegalovirus immediate-early (CMV) promoter and a CAG promoter, and wherein the vector is selected from an AAV2/8 vector, an AAV2/7m8 vector and an AAV9 vector. Also disclosed is a pharmaceutical composition comprising the vector, and use of the vector in a method of treating retinal degeneration associated with BBS comprising administering a therapeutically effective amount of the vector to a patient suffering from BBS, wherein the vector is administered directly to the eye of the patient.