The invention concerns a multicistronic nucleic acid, in particular an isolated multicistronic nucleic acid, comprising: A) a sequence comprising successively: A1) a sequence encoding the light chain variable domain of an antibody of interest, fused in the frame with A2) a sequence encoding the constant region of the light chain of an immunoglobulin Ig; and B) a sequence comprising successively: B1) a sequence encoding the heavy chain variable domain of said antibody of interest, fused in the frame with B2) a sequence encoding the constant regions of the heavy chain of an immunoglobulin Ig′ in secretory form; B3) an intronic sequence of the gene of the heavy chain of said immunoglobulin Ig′, said intronic sequence comprising an internal 5′ splice site enabling the splicing of said intronic sequence B3) and a secretory-specific poly(A) (p AS) signal from the 3′ terminal exon of said gene; B4) a sequence, in frame with sequence B1), encoding the transmembrane and cytoplasmic domains M1 and M2 of the immunoglobulin Ig′ BCR, wherein said sequence B4) comprises, between the coding sequences of the M1 and M2 domains, an intronic sequence containing a splice site enabling the splicing of said intronic sequence between the M1 and M2 domains coding sequences; and B5) a membrane-anchored specific poly(A) signal (p AM), after the stop codon of the M2 domain, wherein the multicistronic nucleic acid enables the co-expression of the sequences A and B into separate proteins.

A human chimeric protein(1) is described, expressed by a viral vector (2) designed for treating patients affected by genetic disorders, composed of a first cDNA sequence [SEQ. 2] of a N-terminal extracellular portion of a human receptor (4) of low-density lipoproteins (5) (hLDLR), fused with a second cDNA sequence [SEQ. 3] of the human transferrin (7) (hTf).

The present invention is directed to improved AAV gene therapy constructs and pharmaceutical compositions for the expression of Kir7.1. The gene therapy constructs are particularly AAV vector comprising a promoter operably connected to a polynucleotide encoding a Kir7.1 polypeptide which is capable of being expressed in retinal pigment epithelium cells. Methods of treating a subject having a condition associated with insufficient expression or function of a Kir7.1 polypeptide are also provided.

Methods and composition for modulating a target genome and stable integration of a transgene of interest into the genome of a cell are disclosed.

The present disclosure provides polynucleotide cassettes, expression vectors and methods for the expression of a gene in mammalian cells to provide gene therapy for pyruvate kinase deficiency.

The application describes ceDNA vectors having linear and continuous structure for delivery and expression of a transgene. ceDNA vectors comprise an expression cassette flanked by two ITR sequences, where the expression cassette encodes a transgene encoding GBA protein. Some ceDNA vectors further comprise cis-regulatory elements, including regulatory switches. Further provided herein are methods and cell lines for reliable gene expression of GBA protein in vitro, ex vivo and in vivo using the ceDNA vectors. Provided herein are method and compositions comprising ceDNA vectors useful for the expression of GBA protein in a cell, tissue or subject, and methods of treatment of diseases with said ceDNA vectors expressing GBA protein. Such GBA protein can be expressed for treating disease, e.g., Gaucher disease.

A construct including a genomic insulator element that exhibits strong enhancer blocking activities in T lymphocytes is provided as are host cells, pharmaceutical compositions and methods of using the construct in the treatment of disease, in particular a disease to be treated with a retroviral vector-modified T lymphocyte.

A polynucleotide comprising a nucleotide sequence encoding an epidermal growth factor receptor (EGFR) extracellular epitope operably linked to: (a) a NGFR or GMS SFR alpha signal peptide; (b) a EGFR or NGFR transmembrane domain; and/or (c) a NGFR or EGFR cytosplasmic tail.

The present invention provides a viral vector comprising a nucleotide sequence encoding a complement protein, wherein the nucleotide sequence is operably linked to a podocyte-specific promoter and/or the viral vector is capable of specifically transducing podocytes.

Adeno-associated virus rh.10 sequences, vectors containing same, and methods of use are provided.