Engineered polypeptides
AssigneeDenali Therapeutics Inc.
InventorsXiaocheng Chen, Mihalis Kariolis, Robert C. Wells
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Abstract
Provided herein are polypeptides that bind to a blood-brain barrier (BBB) receptor, methods of generating such polypeptides, and methods of using the polypeptides to target a composition to a BBB receptor-expressing cell, e.g., for transport across the BBB. Also provided herein are transferrin receptor (TfR) constructs that comprise a monomeric TfR apical domain or one or more portions of the TfR apical domain which have been circularly permuted relative to the full-length TfR sequence.
Claims29
A transferrin receptor (TfR) construct comprising from N- to C-terminus:
- (a) a first polypeptide comprising a C-terminal fragment of a TfR apical domain;
- (b) an optional linker;
- and
- (c) a second polypeptide comprising an N-terminal fragment of the TfR apical domain,
- wherein the first polypeptide, the optional linker, and the second polypeptide are fused in a tandem series.
An isolated, recombinant TfR apical domain construct comprising an amino acid sequence having at least about 90% identity to any one of SEQ ID NOS:109, 110, 301, 468, and 469.
Dependencies are inferred from the claim text.