Antibody fragment degrading and removing abnormal TDP-43
A modified antibody fragment comprising an antibody fragment capable of binding to misfolded TDP-43, and a chaperone-mediated autophagy localizing signal peptide.
1. A modified antibody fragment that binds to misfolded TAR DNA-binding protein of 43 kDa, wherein the modified antibody fragment comprises an antibody fragment and a chaperone-mediated autophagy localizing signal peptide comprising KFREQ (SEQ ID NO: 8) and linked to the C-terminus of the antibody fragment;
the antibody fragment comprising:
a heavy-chain variable region comprising a heavy-chain CDR 1 consisting of an amino acid sequence GFNIKDYY (SEQ ID NO: 1), a heavy-chain CDR 2 consisting of an amino acid sequence IDPEDGET (SEQ ID NO: 2), and a heavy-chain CDR 3 consisting of an amino acid sequence TIIYYYGSRYVDY (SEQ ID NO: 3); and
a light-chain variable region comprising a light-chain CDR 1 consisting of an amino acid sequence SSISSSY (SEQ ID NO: 4), a light-chain CDR 2 consisting of an amino acid sequence RTS, and a light-chain CDR 3 consisting of an amino acid sequence QQGSSIPLT (SEQ ID NO: 5); and
wherein the antibody fragment is a scFv; and
wherein the antibody fragment and the chaperone-mediated autophagy localizing signal peptide are directly bonded, or an amino acid sequence exists between them.
2. The modified antibody fragment according to claim 1 , wherein the antibody fragment is a humanized antibody fragment.
3. A nucleic acid encoding the modified antibody fragment according to claim 1 .
4. An expression vector comprising the nucleic acid according to claim 3 .
5. A method of inducing a heat shock protein in a cell, the method comprising administering the nucleic acid according to claim 3 .
6. The method of claim 5 , wherein the heat-shock protein is Hsp70.