The present invention addresses the issue of providing a norovirus component vaccine for subcutaneous, intradermal, percutaneous, or intramuscular administration which vaccine can readily immunize the target cells, an associated product of a molecular needle serving as an active ingredient of the vaccine, and a production method for the associated product. The invention provides a norovirus component vaccine containing, as an active ingredient, an associated product including a hexamer formed through bonding of two molecules of a trimer of a molecular needle represented by the following formula (1). W-L.sub.1-X.sub.n—Y (1) [wherein W represents an amino acid sequence of P domain of the capsid protein of norovirus as an immunogen; L.sub.1 represents a first linker sequence having 0 to 100 amino acids; X represents an amino acid sequence represented by SEQ ID NO: 1; Y represents an amino acid sequence of a cell introduction domain; n is an integer of 1 to 3].

Aspects of the disclosure relate to methods and compositions useful for in vivo and/or in vitro enzyme profiling. In some embodiments, the disclosure provides methods of in vivo enzymatic processing of exogenous molecules followed by detection of signature molecules as representative of the presence of active enzymes associated with diseases or conditions. In some embodiments, the disclosure provides compositions and in vitro methods for localization of enzymatic activity in a tissue sample.

The present invention provides gene editing systems comprising gene editing dimerization switches comprising a first and second gene editing switch domain that allow for the regulation of a gene editing function by the introduction, e.g., administration, of a gene editing dimerization molecule having the ability to bring together a first gene editing switch domain and a second gene editing switch domain. A regulated gene editing function provides, e.g., less off-target side effects, and increases the therapeutic window.

The present invention also provides improved FKBP/FRB-based dimerization switches wherein the FRB switch domain or the FKBP switch domain, or both the FRB and FKBP switch domains, comprise one or more mutations that optimize performance, e.g., that alter, e.g., enhance the formation of a complex between the first switch domain, the second switch domain, and the dimerization molecule, rapamycin, or a rapalog, e.g., RAD001.

A nucleic acid molecule comprising a nucleotide sequence encoding an inhibitory chimeric antigen receptor (iCAR) capable of preventing or attenuating undesired activation of an effector immune cell, wherein the iCAR comprises an extracellular domain that specifically binds to a single allelic variant of a polymorphic cell surface epitope absent from mammalian tumor cells due to loss of heterozygosity (LOH) but present at least on all cells of related mammalian normal tissue; and an intracellular domain comprising at least one signal transduction element that inhibits an effector immune cell is provided. Vectors and transduced effector immune cells comprising the nucleic acid molecule and methods for treatment of cancer comprising administering the transduced effector immune cells are further provided.

An auxin-inducible degron system kit that controls degradation of a target protein in a non-plant-derived eukaryotic cell, the kit containing a first nucleic acid that encodes a mutant TIR1 family protein having a mutation at an auxin-binding site, an auxin analog that has an affinity to the mutant TIR1 family protein and a second nucleic acid that encodes a degradation tag containing at least a part of an Aux/IAA family protein and having an affinity to a complex of the mutant TIR1 family protein and the auxin analog.

A fluorescent protein of the present invention has an amino acid sequence of a green fluorescent protein (GFP) derived from a crystal jelly or of a mutant fluorescent protein of the green fluorescent protein, the amino acid sequence having an amino acid residue (alanine residue) substituted with a phenylalanine residue, the amino acid residue corresponding to position 206 with the amino acid sequence of the GFP used as a reference sequence.

A novel cytokine-derived cell penetrating peptide and use thereof are provided. The cell penetrating peptide has the ability to effectively deliver a biologically active substance into phagocytes, particularly macrophages, both in vitro and in vivo. The cell penetrating peptide can deliver a biologically active substance into macrophages with high efficiency compared to TAT peptide and dNP2 peptide that are commercially available as cell penetrating peptides.

The present invention is directed to a delivery vector for transferring a small peptide coding sequence to a cell for expression of the small peptide coding sequence within the cell. The delivery vector comprises a secretory signal sequence; a sequence encoding a carrier protein operatively associated with the secretory signal sequence; a sequence encoding a cleavage site operatively associated with the sequence encoding a carrier protein; and a sequence encoding a small peptide operatively associated with the sequence encoding a cleavage site.

The disclosure pertains to the field of molecular means capable of binding to, and preferably of chelating, cGMP, appropriate for use in vitro or in vivo and preferably capable of targeting specific cellular compartments. The polypeptides of the disclosure comprise a chimeric construction derived from the N terminus part of PKG-Iα and PKG-Iβ, and the two cGMP binding sites of the wild type PKG.

The type V-U1 system from the bacterium Mycobacterium mucogenicum CCH10-A2 (Mmu) has a nuclease which binds dsDNA but it does not cleave it. Additionally, after dsDNA binding by the nuclease an RuvC-dependent interference of nascent transcript (mRNA) takes place and this mechanism has not been described before for any CRISPR system. CRISPR based gene manipulation can therefore use CRISPR endonucleases from the Type V-U1 system from Mycobacterium mucogenicum, including variant and modified endonucleases, so as to provide for methods of expression control and gene editing in cells of any living organism or of any nucleic acid in vitro.