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 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.

Methods of preventing or treating rheumatoid arthritis (RA) in a subject by introducing the DRB1*04:01.sup.K71E mutation that is resistant to RA. The resistant allele is introduced into the subject having or at risk of developing RA, using a HLA CRISPR/Cas9 vector that targets codon 71 in the HLA allele DRB1*04:01, introducing a single A to G point mutation in codon 71 by homology directed repair to alter the lysine at position 71 of the expressed protein to glutamic acid. This modified allele is affected in the subject's hematopoietic stem cells, which are then expanded and transplanted back into the patient. This microgene therapy confers RA-resistance via an autologous transplant. The invention includes isolated nucleic acids, vectors, recombinant viruses, cells, and pharmaceutical compositions to modify the HLA DRB1*04:01 allele.

A lentiviral vector system for expressing a lentiviral particle is disclosed. The lentiviral vector system includes a therapeutic vector. The therapeutic vector comprises a phenylalanine hydroxylase (PAH) sequence for expressing at least one of PAH or a variant thereof, wherein the PAH sequence is truncated.

A process for producing blood coagulation Factor VII in 3 human cell lines (HepG2, Sk-Hep, HKB-11) and to select the best recombinant protein producer is described. The murine line BHK-21 was used as control. The data allow to assert that the system used to modify cell lines was efficient, so that all the cells were satisfactorily modified, and produced the protein of interest of stable form. In addition, when comparing the murine line BHK-21 with the human cells (HepG2, Sk-Hep-1 and HKB-11), the latter showed to be able to produce rFVII more efficiently, which allows to conclude that human cell lines are a great alternative for the production of recombinant blood coagulation factors.

A chimeric antigen receptor including: a binding domain, the full DAP 10 protein, the full DAP 12 protein, or a functional variant thereof, and a hook binding domain. Also, a vector system comprising one or more vector including: a nucleic acid comprising a nucleic acid sequence encoding a chimeric antigen receptor and optionally a nucleic acid encoding a hook fusion protein, preferably having a streptavidin core; wherein the nucleic acids are located on the same or on different vectors. Further, a lentiviral vector particles system, host cell and kit including the nucleic acids or vector system, and their use as a medicament, notably for immunotherapy.

Methods of preventing or treating rheumatoid arthritis (RA) in a subject by introducing the DRB1*04:01.sup.K71E mutation that is resistant to RA. The resistant allele is introduced into the subject having or at risk of developing RA, using a HLA CRISPR/Cas9 vector that targets codon 71 in the HLA allele DRB1*04:01, introducing a single A to G point mutation in codon 71 by homology directed repair to alter the lysine at position 71 of the expressed protein to glutamic acid. This modified allele is affected in the subject's hematopoietic stem cells, which are then expanded and transplanted back into the patient. This microgene therapy confers RA-resistance via an autologous transplant. The invention includes isolated nucleic acids, vectors, recombinant viruses, cells, and pharmaceutical compositions to modify the HLA DRB1*04:01 allele.

A synthetic lentiviral vector construct comprises a genomic RNA packaging enhancer (GRPE) element and lentiviral nucleic acid sequences sufficient for reverse transcription and packaging in a host cell.

The present disclosure relates to a novel, engineered enveloped vector that can be used for gene delivery. The engineered enveloped vector comprises an engineered envelope comprising: (a) a viral envelope protein and optionally, (b) a non-viral membrane-bound protein. The present disclosure also provides a method of making and using the engineered enveloped vector.

Disclosed herein are compositions and methods that can be used to express a nucleotide sequence in a specific cell type. The compositions can comprise nucleic acid constructs comprising a start codon; and an intron cassette. The intron cassette can comprise a cell specific exon sequence, a splice donor site, a branch site, and an acceptor site. The cell specific exon sequence is out of frame with the start codon and comprises one or more frameshift mutations. The compositions can be used to treat human diseases.

The present invention provides compositions and methods for transducing cells (e.g. T cells or immune cells). Also provided herein are methods of treating a disease in a subject in need thereof.