Single chain intrabodies that alter huntingtin mutant degradation
AssigneeVybion, Inc.
InventorsLee Alan Henderson, Irene Alexandra Amaro
Life of this patent
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Abstract
Compositions and methods of use are provided for intrabodies that bind and alter the effects of poly-glutamate protein aggregation in poly-glutamate associated diseases, such as in Huntington's disease. Intrabodies are provided that prevent poly-glutamate aggregation, gene dysregulation, and negative effects of Huntington's disease.
Claims10
A method of treating or managing a subject having a disease associated with aggregation of Huntingtin protein in a cell, wherein the disease associated with aggregation of Huntington protein is Huntington's disease, comprising administering to a subject in need of such treatment or management a therapeutically effective amount of an intrabody comprising an amino acid sequence comprising:
- a variable heavy sequence, a variable light chain sequence, and a linker sequence interposed between the variable heavy sequence and the variable light sequence, wherein the variable heavy sequence comprises:
- a variable heavy complementarity-determining region (CDR) 1 sequence comprising SEQ ID NO:
- 21, a variable heavy CDR2 sequence comprising SEQ ID NO:
- 22, and a variable heavy CDR3 sequence comprising SEQ ID NO:
- 6;
- and wherein the variable light sequence comprises:
- a variable light CDR1 sequence comprising SEQ ID NO:
- 23, a variable light CDR2 sequence comprising SEQ ID NO:
- 24, and a variable light CDR3 sequence comprising SEQ ID NO:
- 10.
A method for inhibiting aggregation of Huntingtin protein in a cell, comprising:
- (a) introducing into the cell a single chain intrabody comprising an amino acid sequence comprising:
- a variable heavy sequence, a variable light chain sequence, and a linker sequence interposed between the variable heavy sequence and the variable light sequence,
- wherein the variable heavy sequence comprises:
- a variable heavy CDR1 sequence comprising SEQ ID NO:
- 21, a variable heavy CDR2 sequence comprising SEQ ID NO:
- 22, and a variable heavy CDR3 sequence comprising SEQ ID NO:
- 6;
- and
- the variable light sequence comprises:
- a variable light CDR1 sequence comprising SEQ ID NO:
- 23, a variable light CDR2 sequence comprising SEQ ID NO:
- 24, and a variable light CDR3 sequence comprising SEQ ID NO:
- 10;
- and
- (b) maintaining the cell produced in step (a) for a time sufficient for the intrabody to bind to the Huntingtin protein, thereby preventing aggregation of Huntingtin proteins in the cell.
A method for inhibiting gene dysregulation caused by aggregation of Huntingtin protein in a cell, comprising:
- (a) introducing into the cell an intrabody comprising an amino acid sequence comprising:
- a variable heavy sequence, a variable light chain sequence, and a linker sequence interposed between the variable heavy sequence and the variable light sequence,
- wherein the variable heavy sequence comprises:
- a variable heavy CDR1 sequence comprising SEQ ID NO:
- 21, a variable heavy CDR2 sequence comprising SEQ ID NO:
- 22, and a variable heavy CDR3 sequence comprising SEQ ID NO:
- 6;
- and
- the variable light sequence comprises:
- a variable light CDR1 sequence comprising SEQ ID NO:
- 23, a variable light CDR2 sequence comprising SEQ ID NO:
- 24, and a variable light CDR3 sequence comprising SEQ ID NO:
- 10;
- and
- (b) maintaining the cell produced in step (a) for a time sufficient for the intrabody to bind to the Huntingtin protein, thereby preventing gene dysregulation of one or more genes in the cell.
Dependencies are inferred from the claim text.