Targeting the secreted ige poly-a signal allows specific inhibition of allergen-specific ige production

Immunoglobulins (Ig) are expressed either on the surface of B cells or as secreted antibodies by plasma cells that represents the final stage of B cell differentiation. The present invention involves the use of antisense oligonucleotides (ASOs) for either reducing the production of the secreted form or either reducing the production of the membrane form. In particular, the inventors show that antisense oligonucleotides masking the secretory polyadenylation signal induce a decrease in the production of the secreted immunoglobulin. Inversely, antisense oligonucleotides masking the membrane polyadenylation signal induce a decrease in the production of the membrane-anchored immunoglobulin. The proof of concept has been obtained using an ASO hybridizing to the polyadenylation signal (PAS) sequence of the transcript encoding the secreted form of IgE. Indeed, the targeting of this PAS sequence induces a drastic decrease in IgE production. Thus the choice of the right antisense oligonucleotide would be suitable for the treatment of diseases associated to B-cell development (e.g. autoimmune diseases, inflammation or B-cell malignancies).

Keywords: Antisens oligonucleotide, Immunoglobulin, Allergy, B Cell Lymphomas
Patent Application number: PCT/EP2020/065327
J Allergy Clin Immunol. 2022 May;149(5):1795-1801. doi: 10.1016/j.jaci.2021.09.039. Epub 2021 Nov 2

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