Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Universite Claude Bernard – Lyon1

Ecole Normale Superieure De Lyon

Thierry Defrance

Els Verhoeyen

François-Loïc Cosset

Floriane Fusil

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&#x2032;, said intronic sequence comprising an internal 5&#x2032; splice site enabling the splicing of said intronic sequence B3) and a secretory-specific poly(A) (p AS) signal from the 3&#x2032; 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&#x2032; 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.

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Lyons, France

Thierry Defrance