Provided herein are vaccine composition comprising an antigen conjugated to a capsid, wherein the capsid comprises wild type or native sequence. Provided herein are also vaccine composition comprising an antigen conjugated to a capsid, wherein said capsid comprises at least one mutation, such as a non-natural mutation. Such compositions are useful in the treatment and prevention of pathogenic infections, inflammatory diseases, and neurodegenerative disease, and cancer, among others.

A method for producing genetically engineered immune cells, e.g. T cells, or iPSCs which uses an RNA-scaffold mediated base editing system. The method enables precise modifications to be made to the genome whilst minimizing the possibility of off-target effects, making the method particularly suitable for therapeutic applications.

A factor that is caused by a nucleic acid and influences the kinetics of an extracellular vesicle is screened. A library of barcoded extracellular vesicles is provided.

Aspects of the disclosure relate to a gene therapy approach for diseases, disorders, or conditions caused by mutation in the stop codon utilizing modified tRNA. At least 10-15% of all genetic diseases, including muscular dystrophy (e.g. Duchene muscular dystrophy), some cancers, beta thalassemia, Hurler syndrome, and cystic fibrosis, fall into this category. Not to be bound by theory, it is believed that this approach is safer than CRISPR approaches due to minimal off-target effects and the lack of genome level changes.

An immunogen generally includes a virus-like particle and an antigen linked to the virus-like particle. The antigen includes an antigenic portion of a polypeptide, wherein the polypeptide inhibits lipoprotein lipase (LPL) activity by binding to LPL. In some embodiments, the polypeptide is at least a portion of angiopoietin-like 3 (ANGPTL3). In other embodiments, the polypeptide is at least a portion of angiopoietin-like 4 (ANGPTL4). In other embodiments, the polypeptide at least a portion of angiopoietin-like 8 (ANGPTL8). In some embodiments, the virus-like particle is a Qbeta immunogenic carrier. In some of these embodiments, the antigen is linked to the virus-like particle through a Gly-Gly-Gly-Cys linker at the C-terminal of the antigen.

Aspects of the disclosure relate to a gene therapy approach for diseases, disorders, or conditions caused by mutation in the stop codon utilizing modified tRNA. At least 10-15% of all genetic diseases, including muscular dystrophy (e.g. Duchene muscular dystrophy), some cancers, beta thalassemia, Hurler syndrome, and cystic fibrosis, fall into this category. Not to be bound by theory, it is believed that this approach is safer than CRISPR approaches due to minimal off-target effects and the lack of genome level changes.

Provided herein are delivery particle systems (XDP) useful for the delivery of payloads of any type. In some embodiments, a XDP particle system with tropism for target cells of interest is used to deliver CRISPR/Cas polypeptides (e.g., CasX proteins) and guide nucleic acids (gNA), for the modification of nucleic acids in target cells. Also provided are methods of making and using such XDP to modify the nucleic acids in such cells.

Novel processes and compositions are described which use viral capsid proteins resistant to hydrolases to prepare virus-like particles to enclose and subsequently isolate and purify target cargo molecules of interest including nucleic acids such as siRNAs and shRNAs, miRNAs, messenger RNAs, small peptides and bioactive molecules.

Methods and materials for improved delivery of dsRNA are presented. In particular, methods for controlling an insect pest by stably delivering large quantities of dsRNA to the insect pest are provided. Compositions comprising a bacterium containing a large quantity of dsRNA targeting an insect gene in which the dsRNA exhibits increased stability and activity are also provided.

The invention provides methods and compositions for improved production of large quantities of unencapsidated doublestrand RNA (dsRNA) in vivo. The disclosed methods and compositions, comprising co-expression of genes encoding orotate phospori-bosyl transferase, bacteriophage coat protein and dsRNA produce a significant improvement over current in vivo methods of producing unencapsidated dsRNA.