The present disclosure provides codon optimized nucleotide sequences encoding human alpha-galactosidase A, vectors, and host cells comprising codon optimized alpha-galactosidase A sequences, and methods of treating disorders such as Fabry disease comprising administering to the subject a codon optimized sequence encoding human alpha-galactosidase A.

Compositions for the treatment of hemophilia B are provided. In certain embodiments, the composition is a recombinant adeno-associated virus (rAAV) comprising an AAVrh10 capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5′ inverted terminal repeat (ITR), a coding sequence for a human Factor IX (F9) having coagulation function operably linked to regulatory elements which direct expression of the human Factor IX in liver cells, and an AAV 3′ ITR.

The present invention provides compositions comprising nucleic acid molecules, such as mRNA molecules, encapsulated within lipid particles. The compositions are useful, for example, to introduce the mRNA molecules into a human subject where they are translated to produce a polypeptide that functions to ameliorate one or more symptoms of a disease.

A method to prevent, inhibit or treat one or more symptoms associated with disease of the central nervous system by intranasally, intrathecally, intracerebrcvascularly or intravenously administering a rAAV encoding a gene product associated with the disease, e.g., a mammal in which the gene product is absent or present at a reduced level relative to a mammal without the disease, in an amount effective, e.g., to provide for cross-correction.

The present invention relates to a pharmaceutical composition comprising a modified mRNA that is stabilised by sequence modifications and optimised for translation. The pharmaceutical composition according to the invention is particularly well suited for use as an inoculating agent, as well as a therapeutic agent for tissue regeneration. In addition, a process is described for determining sequence modifications that promote stabilisation and translational efficiency of modified mRNA of the invention.

The present invention relates to methods for administering autologous and/or allogeneic B cells genetically modified to produce a therapeutic agent, such as a therapeutic protein. Specifically disclosed are methods for administering a single, maximally effective dose of genetically modified B cells and for administering multiple doses of genetically modified B cells. The compositions and methods disclosed herein are useful for the long-term, in vivo delivery of a therapeutic agent.

Disclosed herein are methods and compositions comprising an adeno-associated vims 2.5 (AAV2.5) capsid protein, comprising one or more amino acids substitutions, wherein the substitutions introduce a new glycan binding site into the AAV capsid protein.

Disclosed are methods for treating an individual with a chemotherapy-resistant primary and/or secondary malignancy that comprise administering a therapeutically effective amount of a tumor-targeted retrovector encoding a cytocidal dominant-negative Cyclin G1 construct, such as DeltaRex-G, to the individual. Also disclosed are methods in which DeltaRex-G, either alone or in conjunction with other cancer therapies and/or treatments, may be administered to ameliorate or eliminate the life-threatening effects of metastatic cancer.

Provided herein are methods and constructs comprising close-ended DNA (ceDNA vectors) for maintaining or sustaining a level of transgene expression at a predetermined level or range for a predefined time, or increasing the level of transgene expression in a cell or a subject, where the transgene expression level can be modulated (e.g., increased) with one or more subsequent administrations (e.g., a re-dose or a booster administration) after an initial priming administration. Provided are methods for personalizing gene therapy throughout an individuals' lifespan to express a transgene at a level that meets an individual's needs, by modulating expression levels of a transgene expressed by ceDNA vector incrementally, or in a step-by-step manner, with one or more administrations after an initial priming administration (e.g., at time 0), thereby enabling titration of the level of expression of the transgene to a desired predetermined expression level or to a desired expression level range.

The present invention relates to compositions and methods comprising administering gene modifiers for treating ocular disease.