The present disclosure relates to methods and agents for antigen vaccination and inducing effective antigen-specific immune effector cell responses such as T cell responses. These methods and agents are, in particular, useful for the treatment of diseases characterized by diseased cells expressing an antigen the immune effector cells are directed to. In some embodiments, the present disclosure relates to methods comprising administering to a subject (i) non-immunogenic RNA encoding a peptide or polypeptide comprising an epitope for inducing an immune response against an antigen in the subject, i.e., non-immunogenic RNA encoding vaccine antigen; and (ii) a PD-1 axis binding antagonist such as an anti-PD-1 antibody and/or an anti-PD-L1 antibody.

The present disclosure relates, in part, to siloxane-based lipids or lipidoids, lipid nanoparticles (LNPs) comprising the same, and pharmaceutical compositions thereof. In certain embodiments, the LNPs of the present disclosure selectively target cells (e.g., hepatocytes, epithelial cells, endothelial cells, and immune cells, inter alia) and/or organs of interest (e.g., liver, spleen, heart, and lungs, inter alia). In another aspect, the present disclosure relates to methods of treating, preventing, and/or ameliorating one or more diseases and/or disorders in a subject, the method comprising administering to the subject at least one LNP of the present disclosure and/or at least one pharmaceutical composition of the present disclosure.

The disclosure relates generally to tRNA-based effector molecules (TREMs) and compositions thereof useful for the treatment or prevention of a proliferative disease or disorder (e.g., a cancer) in a subject.

This application provides improved methods of genome editing. Cas9 molecules can be used to create a break in a genomic region of interest. To increase the likelihood that the break is repaired by HDR (homology-directed repair), the cell can be contacted with molecules that bring a template nucleic acid in close proximity to the break, under conditions that allow the cell to repair the break using the template nucleic acid.

Circular RNA, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes an antigen. In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.