Disclosed is a fully human antibody specifically inhibiting a connexin 26. The antibody is a recombinant immunoglobulin having the structure of scFv-Fc. scFv refers to a single-chain antibody comprising a heavy chain variable region and a light chain variable region, wherein the amino acid sequence of the heavy chain variable region is set forth in SEQ ID NO: 1 and the amino acid sequence of the light chain variable region is set forth in SEQ ID NO: 2. Fc refers to a constant region. An amino acid sequence from the 41st to the 56th amino acids in an extracellular region of human connexin 26, i.e., KEVWGDEQADFVCNTL, is used as an antigen. The invention is obtained by employing a single-chain antibody phage display library and a screening technique. A biochemical analysis and an immunofluorescent identification of the antibody indicated that the antibody specifically recognizes the connexin 26 and inhibits an activity of a hemichannel formed by the connexin 26. An animal test showed that the antibody exerted a significant inhibitory effect on the activity of a hemichannel in a murine cochlear tissue slice. Therefore, the antibody can be used for the treatment of a disease associated with connexin mutation.

Fully human antibody specifically inhibiting connexin 26

MAMMANO Fabio
Conceptualization
;
ZONTA Francesco
Conceptualization
2017

Abstract

Disclosed is a fully human antibody specifically inhibiting a connexin 26. The antibody is a recombinant immunoglobulin having the structure of scFv-Fc. scFv refers to a single-chain antibody comprising a heavy chain variable region and a light chain variable region, wherein the amino acid sequence of the heavy chain variable region is set forth in SEQ ID NO: 1 and the amino acid sequence of the light chain variable region is set forth in SEQ ID NO: 2. Fc refers to a constant region. An amino acid sequence from the 41st to the 56th amino acids in an extracellular region of human connexin 26, i.e., KEVWGDEQADFVCNTL, is used as an antigen. The invention is obtained by employing a single-chain antibody phage display library and a screening technique. A biochemical analysis and an immunofluorescent identification of the antibody indicated that the antibody specifically recognizes the connexin 26 and inhibits an activity of a hemichannel formed by the connexin 26. An animal test showed that the antibody exerted a significant inhibitory effect on the activity of a hemichannel in a murine cochlear tissue slice. Therefore, the antibody can be used for the treatment of a disease associated with connexin mutation.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3257872
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