The application discloses multimeric assemblies including multiple oligomeric substructures, where each oligomeric substructure includes multiple proteins that self-interact around at least one axis of rotational symmetry, where each protein includes one or more polypeptide-polypeptide interface (“O interface”); and one or more polypeptide domain that is capable of effecting membrane scission and release of an enveloped multimeric assembly from a cell by recruiting the ESCRT machinery to the site of budding by binding to one or more proteins in the eukaryotic ESCRT complex (“L domain”); and where the multimeric assembly includes one or more subunits comprising one or more polypeptide domain that is capable of interacting with a lipid bilayer (“M domain”), as well as membrane-enveloped versions of the multimeric assemblies.

Provided herein are bifunctional lysosomal targeting degraders including a ligand configured to bind to transferrin receptor as a shuttle molecule for lysosome degradation, and a protein-binding moiety configured to bind a membrane or extracellular protein of interest, wherein the bifunctional lysosome targeting degraders can be recycled back out of cells and be catalytic. The bifunctional degraders find use, e.g., for selectively targeted degradation of membrane or extracellular proteins via the endosomal/lysosomal pathway. Also provided herein are compositions comprising the bifunctional degraders, as well as methods of using the bifunctional degraders.

[Problem] To provide a nucleic acid expected to be useful for treating mite allergy.

[Means to be solved] Provided is a nucleic acid comprising a nucleotide sequence encoding a chimeric protein, wherein the nucleic acid comprises a nucleotide sequence encoding a signal peptide, a nucleotide sequence encoding an intra-organelle stabilizing domain of LAMP, a nucleotide sequence encoding an allergen domain comprising Der p 1, Der p 2, Der p 23, and Der p 7, a nucleotide sequence encoding a transmembrane domain and a nucleotide sequence encoding an endosomal/lysosomal targeting domain of LAMP in this order.

A CRISPR/Cas system and method for editing or regulating transcription of a genome of a cell are provided, wherein the system includes a Cas endonuclease fused with one or more degron sequences and at least one activatable cognate single guide RNA harboring an inactivation sequence in a non-essential region of the cognate sgRNA, wherein said inactivation sequence comprises one or more endonuclease recognition sites of, e.g., a ribozyme.

The application discloses multimeric assemblies including multiple oligomeric substructures, where each oligomeric substructure includes multiple proteins that self-interact around at least one axis of rotational symmetry, where each protein includes one or more polypeptide-polypeptide interface (“O interface”); and one or more polypeptide domain that is capable of effecting membrane scission and release of an enveloped multimeric assembly from a cell by recruiting the ESCRT machinery to the site of budding by binding to one or more proteins in the eukaryotic ESCRT complex (“L domain”); and where the multimeric assembly includes one or more subunits comprising one or more polypeptide domain that is capable of interacting with a lipid bilayer (“M domain”), as well as membrane-enveloped versions of the multimeric assemblies.

The present invention provides vaccines against respiratory viruses including coronavirus, such as SARS-CoV-2, and influenza viruses. In particular, the present invention provides vaccines against SARS-CoV-2 which encode a targeting domain and a SARS-CoV-2 spike protein or fragment thereof.

The present disclosure provides CasX proteins, nucleic acids encoding the CasX proteins, and modified host cells comprising the CasX proteins and/or nucleic acids encoding same. CasX proteins are useful in a variety of applications, which are provided. The present disclosure provides CasX guide RNAs that bind to and provide sequence specificity to the CasX proteins, nucleic acids encoding the CasX guide RNAs, and modified host cells comprising the CasX guide RNAs and/or nucleic acids encoding same. CasX guide RNAs are useful in a variety of applications, which are provided. The present disclosure provides archaeal Cas9 polypeptides and nucleic acids encoding same, as well as their associated archaeal Cas9 guide RNAs and nucleic acids encoding same.

The present invention provides DNA vaccines for the treatment or prevention of an allergic response. The vaccines comprise the coding sequence for Allergen X or fragments thereof fused in-frame with the lumenal domain of the lysosomal associated membrane protein (LAMP) and the targeting sequence of LAMP. The vaccines allow for presentation of properly configured three dimensional epitopes for production of an immune response when administered to a subject. The vaccines can be multivalent molecules, and/or can be provided as part of a multivalent vaccine containing two or more DNA constructs.

The present invention relates to variants of acid-alpha glucosidase and uses thereof.

Nucleic acids (also referred to herein as “constructs”) that encode allergenic proteins, allergenic polypeptides, and allergenic peptides are provided. The nucleic acids are designed for delivery to immune cells and production of allergenic proteins, polypeptides, and peptides within those cells. The encoded proteins, polypeptides, and peptides have targeting sequences for targeting of the proteins to the MHC-II compartment for processing and display of one or more epitopes, resulting in an immune response to the epitope(s). In general, the nucleic acids comprise the following domains, which correlate to the respective domains of the encoded protein: a signal sequence domain; an intra-organelle stabilizing domain; an allergen domain; a transmembrane domain; and a cytoplasmic lysosome/endosome targeting domain.