The present disclosure relates to a method for constructing a producer cell and the producer cell obtained by the method, wherein the producer cell is for producing a retroviral vector carrying a nucleic acid fragment of interest.

We disclose a lentiviral vector, for use in research, clinical, industrial, and other suitable applications. The novel lentiviral vectors disclosed herein introduce numerous novel elements which increase the safety profile of the vector without reducing the efficacy of the system. The novel lentiviral vectors are useful as safe and highly efficient transduction vectors for any application using or benefitting from transduction.

The present invention discloses cell lines and recombinant growth factor receptors useful in adoptive cell therapy (ACT), wherein the recombinant growth factor receptor can act as a molecular switch enabling cells expressing the rGFR protein to be expanded in-vitro or in-vivo. Thus the invention provides a T or NK cell, comprising a recombinant growth factor receptor (rGFR) comprising: (i) an extracellular (EC) domain; (ii) a thrombopoietin receptor transmembrane (TM) domain; and (iii) a growth factor receptor intracellular (IC) domain.

The present invention discloses cell lines and recombinant growth factor receptors useful in adoptive cell therapy (ACT), wherein the recombinant growth factor receptor can act as a molecular switch enabling cells expressing the rGFR protein to be expanded in-vitro or in- vivo. Thus the invention provides a T or NK cell, comprising a recombinant growth factor receptor (rGFR) comprising: (i) an extracellular (EC) domain; (ii) a thrombopoietin receptor transmembrane (TM) domain; and (iii) a growth factor receptor intracellular (IC) domain.

The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises a mitogenic T-cell activating transmembrane protein which comprises: (i) a mitogenic domain which binds a mitogenic tetraspanin, and (ii) a transmembrane domain; wherein the mitogenic T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells or Natural Killer cells are transduced by such a viral vector, they are activated by the mitogenic T-cell activating transmembrane protein.

Provided is a chimeric antigen receptor targeting CLL1 and an application thereof. The chimeric antigen receptor targeting CLL1 comprises an antigen binding domain, a hinge region, a transmembrane domain and a signal transduction domain; the antigen binding domain is an anti-CLL1 antibody. The present application uses an anti-CLL1 antibody as the antigen binding domain to construct a chimeric antigen receptor molecule, the chimeric antigen receptor targeting CLL1 has specific targeting effect on CLL1 positive tumor cells, and immune cells expressing chimeric antigen receptor targeting CLL1 have a significant killing effect in vitro and in vivo, and secrete a large amount of cytokine IFN-γ after co-cultured with CLL1 positive tumor cells, which has a specific clearance effect on CLL1 positive tumor cells.

Provided is a viral particle comprising a genomic RNA suitable for delivering a polynucleotide sequence of interest (SOI) into a cell and/or a subject. The genomic RNA comprises, from 5′ to 3′: (a) the SOI replacing the upstream R, (b) a U5, (c) a primer binding site (PBS), (d) an encapsidation signal (Psi), (e) polypurine tract(s) (PPT), and (f) a U3. The SOI preferably takes the form of single-stranded DNA or a DNA-RNA hybrid after initiation of reverse transcription. Additionally provided are polynucleotides, vectors, cells, components, compositions, kits, methods and uses of the viral particle.

The present invention relates generally to immunization and immunotherapy for the treatment or prevention of HIV. In particular, the methods include in vivo and/or ex vivo enrichment of HIV-specific CD4+ T cells.

Recombinant vectors containing at least: a backbone comprising essential sequences for integration into a target cell genome; a nucleic acid encoding a CCR5 RNAi operatively linked to a a first expression control element that regulates expression of the nucleic acid encoding the RNAi of the CCR5; a nucleic acid encoding at least the extracellular domain of CD25 operatively linked to a second expression control element that regulates expression of the nucleic acid encoding at least the extracellular domain of CD25 are provided by this disclosure. In an alternative aspect, the vector also contains polynucleotides encoding TRIM5alpha and HIV TAR decoy sequences along with gene expression regulation elements such as promoters operatively linked to the polynucleotides. The vectors are combined with packaging plasmid and envelope plasmids and optionally conjugated to cell-specific targeting antibodies. Diagnostic and therapeutic methods for using the compositions are further provided herein.

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.