Methods are described for predicting ancestral sequences for viruses or portions thereof. Also described are predicted ancestral sequences for adeno-associated virus (AAV) capsid polypeptides. The disclosure also provides methods of gene transfer and methods of vaccinating subjects by administering a target antigen operably linked to the AAV capsid polypeptides.

The present invention relates to methods for treating facioscapulohumeral dystrophy (FSHD). Specifically, the invention relates to the use of an inhibitor of necroptosis for treating FSHD.

The present invention provides novel systems, methods and compositions for making and using a recombinantly engineered novel Cas9 optimized for human cells, for nucleic acid targeting and manipulation. The present invention is based on the discovery of a novel Cas9 species from Lachnospira bacterium that was codon-optimized and recombinantly produced for use in human ceils. In some embodiments, the novel Cas9 can be used in a base editor. In some embodiments, the novel engineered Cas9 is used to treat human diseases.

Provided herein are methods for the production of recombinant adeno-associated virus (rAAV) particles. These methods are particularly useful for the large-scale production of AAV particles.

A method for slowing the progression of amyotrophic lateral sclerosis (ALS) in an adult subject in need thereof is provided herein, the method including inhibiting motor neuron degeneration by administering to the subject a modified adeno-associated virus (AAV) vector having a recombinant AAV (rAAV)-based genome with an AAV backbone, a control element, and a ciliary neurotrophic factor receptor alpha (CNTFRα) cDNA insert, wherein the modified AAV vector is engineered to direct enhanced skeletal muscle expression of CNTFRα.

The present invention relates to a modified and optimized sFlt1 nucleic acid for inclusion in a virus vector. Use of such vectors can be used for treatment of ocular disorders causing neovascularization, such as macular degeneration.

Provided herein are methods and related compositions for administering viral transfer vectors and antigen-presenting cell targeted immunosuppressants.

Methods of the invention encompass delivery of nucleic acid sequences encoding ABCD1 for the treatment of X-linked Adrenoleukodystrophy (X-ALD), e.g., for Adrenomyeloneuropathy (AMN).

The present invention relates to an adeno-associated vims (AAV) or an adeno-associated virus-like particle (AAVLP), comprising an insert of about 75-400 amino acids in the viral proteins (VPs) VP1, VP2 and/or VP3 at an insertion site (I) at the top of variable region VIII and/or variable region IV (VR-VIII and/or VR-IV) of the VP, wherein the insert is an immunogenic protein or a portion thereof and/or wherein the insert is a protein comprising a binding domain, such as an antigen-binding domain specific for a target antigen. The present invention also relates to pharmaceutical compositions comprising said AAV or AAVLP and to the pharmaceutical composition or the AAV or AAVLP for use in therapy, particularly for use as a vaccine, for use in the treatment or the prevention of a diseases and/or for use in gene therapy. Also concerned is a method for producing the AAV of AAVLP of the present invention.

The present disclosure provides a variant AAV capsid protein that confers tropism to lung cells and recombinant adeno-associated viruses comprising the variant AAV and pharmaceutical compositions comprising same and their use in the delivery of heterologous nucleic acids to lung cells for the treatment of pulmonary disorders.