Lentiviral vector expressing membrane-anchored or secreted antibody

Abstract

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.