This disclosure provides compositions and methods for delivering a viral composition to cells, e.g., for cell surface receptor-mediated uptake, and enhanced viral transduction. Viral transduction can be achieved via a bifunctional bridging composition that includes a moiety that binds to a cell surface receptor ligand and a linked bridging moiety that binds to a viral composition. Also provided are modified viral compositions comprising a bridging composition specifically bound via its bridging moiety to the viral composition. Modified viral compositions and methods for reducing levels or titers of neutralizing antibodies in a subject in need of viral therapy, e.g., gene therapy, are provided. In some embodiments, the modified viral composition includes empty viral particles that bind and internalize neutralizing autoantibodies. Modified viral compositions including empty viral particles can be administered prior to viral therapy. Also provided are pharmaceutical compositions and kits including a bifunctional bridging composition and/or modified viral compositions.

A method of preparing a chimeric virus comprising bocavirus capsid protein (VP) and a recombinant adeno-associated (AAV) viral genome, and isolated mutant bocavirus genomes, are provided.

A method for the systemic delivery of a polypeptide within a subject is provided by creating genetically modified skin cells via topical introduction of a genetically engineered virus which delivers a nucleic acid encoding a therapeutic polypeptide for expression by the skin cells, wherein the expressed therapeutic polypeptide is secreted by the skin cells and is introduced into the circulatory system of the subject.

The present invention provides a polyploid adeno-associated virus (AAV) capsid, wherein the capsid comprises capsid protein VP1, wherein said capsid protein VP1 is from one or more than one first AAV serotype, wherein said capsid protein VP2 is from one or more than one first AAV serotype and capsid protein VP3, wherein said capsid protein VP3 is from one or more than one second AAV serotype and wherein at least one of said first AAV serotype is different from at least one of said second AAV serotype and is different from at least one of said third AAV serotype, in any combination.

Genetically modified compositions, such as adeno-associated viral vectors and primary cells, for treating various conditions and diseases. Disclosed are also modified adeno-associated viruses for the treatment of cancer. Also disclosed are the methods of making and using the genetically modified compositions in treating various diseases, conditions, and cancer.

Disclosed herein are methods and compositions for gene therapy, in particular, methods and compositions related to alterations in a capsid protein sequence for altering permissiveness of a promoter within a cell when the promoter and the capsid protein are present within the cell and the capsid protein and the promoter are in the context of a recombinant adeno-associated virus (AAV) particle.

Non-human animal cells and non-human animals comprising a humanized Asgr1 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized Asgr1 locus express a human ASGR1 protein or an Asgr1 protein, fragments of which are from human ASGR1. Methods are provided for using such non-human animals comprising a humanized Asgr1 locus to assess in vivo efficacy of human-ASGR1-mediated delivery of therapeutic molecules or therapeutic complexes to the liver and to assess the efficacy of therapeutic molecules or therapeutic complexes acting via human-ASGR1-mediated mechanisms.

Provided are an AAV capsid protein mutant and an encoding nucleic acid, and a corresponding vector and a host cell thereof. Also provided are an adeno-associated virus vector containing the AAV capsid protein mutant, a recombinant adeno-associated virus particle constructed therefrom and carrying a gene expression cassette, a preparation method therefor, and the use thereof in treating diseases.

The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

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