A modified U1 snRNA, wherein said modified U1 snRNA has been modified to bind to a nucleotide sequence within the packaging region of a lentiviral vector genome sequence.

Objects to be achieved are to provide a nerve cell with which it is possible to visualize and quantify the intracellular tau without using the exogenous promoter and to provide a pluripotent stem cell with which the nerve cell can be produced, to provide a method of screening a substance, including using the pluripotent stem cell or nerve cell described above, and a substance screened by the above method, and to provide a kit including a targeting vector and a gRNA.

There is provided a pluripotent stem cell including a DNA encoding a reporter molecule, the DNA being introduced adjacent to an endogenous tau gene such that a tau protein is expressed as a fusion protein fused with a reporter molecule.

The invention relates to a recombinant lentiviral vector genome comprising a polynucleotide encoding a fusion polypeptide, wherein said fusion protein comprises arranged from N-terminal to C-terminal ends: (i) a first polypeptide comprising a multimerization scaffold which comprises at least one collectin or a fragment thereof suitable to enable self-assembly of multimers of the first polypeptide, fused with at least one antigenic polypeptide; (ii) a second polypeptide comprising a CD40L ectodomain or a receptor binding fragment thereof, in particular the CD40L ectodomain of the human CD40L. The invention also relates to a lentiviral vector and pharmaceutical compositions comprising it.

The present invention provides a chimeric antigen receptor, which includes: an extracellular domain, a transmembrane domain, and an intracellular domain connected in sequence. The extracellular domain includes an antigen recognition region; the intracellular domain includes a costimulatory signaling region and a CD3ζ intracellular region that are connected in sequence, to form a costimulatory signaling region-CD3ζ intracellular region; and the costimulatory signaling region-CD3ζ intracellular region is a polypeptide formed by mutation of lysine in a wild-type costimulatory signaling region-CD3ζ intracellular region into arginine. The present invention provides a method for optimization and modification of CAR-T, in which all lysine sites in an intracellular segment of CAR are mutated into arginine, thereby blocking ubiquitination modification of the CAR after antigen challenge. This strategy is applicable to different CARs and changing different intracellular costimulatory domains, and in particular provides a solution to the problem of poor proliferation of CAR-T in solid tumors.

The invention features pseudotyped viral particles (e.g., lentiviral or gammaretroviral particles) and compositions and methods of use thereof, where the viral particles comprise a VHH domain.

The invention features pseudotyped viral particles (e.g., lentiviral or gammaretroviral particles) and compositions and methods of use thereof, where the viral particles comprise a VHH domain.

The present invention relates to a novel closed linear DNA vector, which is suitable for use in the production of lentiviral particles. Notably, the present invention relates to a new configuration of the vector including the transgene (often termed the payload vector), which enables a greater yield of infectious lentiviral particles, notably a greater yield of lentiviral particles carrying a trans-gene, to be prepared when compared to closed linear DNA vectors lacking this configuration. Further, the inventors have developed improvements in lentiviral production with closed linear DNA, through optimisation of vector input quantities and construct ratios. The invention furthermore relates to a method of generating infectious lentiviral particles using the construct, optionally in conjunction with improved production vectors and/or optimised methodology.