Engineered botulinum neurotoxin
AssigneePresident and Fellows of Harvard College
InventorsMin Dong, Lisheng Peng, Liang Tao
Life of this patent
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Abstract
Disclosed herein is a botulinum neurotoxin (BoNT) polypeptide with a modified receptor binding domain (HC) having one or more amino acid mutations that modify the binding of the BoNT to the receptor. Specific mutations and combinations of mutations are also disclosed. Isolated modified HC, polypeptides comprising the modified HC, chimeric molecules, pharmaceutical compositions, and methods of making and using the same are also disclosed. Methods of identifying additional such modified receptor binding domains, are further disclosed.
Claims13
A nucleic acid comprising a nucleotide sequence that encodes a polypeptide comprising a modified receptor binding domain of Clostridial botulinum serotype B (B-Hc), wherein the modified B-Hc comprises two or more amino acid substitutions relative to a reference wild type receptor binding domain of a C. botulinum serotype B, strain 1 as found in SEQ ID NO:
- 5, wherein the two or more amino acid substitutions are at positions selected from the group consisting of E1191, S1199, W1178, Y1183, and combinations thereof, wherein:
- the substitution at position E1191 is E1191A;
- the substitution at position S1199 is selected from the group consisting of S1199W, S1199E, and S1199H;
- the substitution at position W1178 is selected from the group consisting of W1178Y, W1178Q, W1178A, and W1178S;
- and
- the substitution at position Y1183 is selected from the group consisting of Y1183C, and Y1183P, and
- wherein the polypeptide is characterized by enhanced binding to human Syt II as compared to that observed with the reference wild type receptor binding domain.
Dependencies are inferred from the claim text.