Abstract: The present disclosure includes engineering methods and polypeptide libraries that are useful for introducing non-native binding sites into polypeptides. Also provided herein are polypeptides that bind to a CD98hc or transferrin receptor (TfR) protein, methods of generating such polypeptides, and methods of using the polypeptides to target a composition across the blood-brain barrier or to a CD98hc-expressing or TfR-expressing cell.

Abstract: Provided herein are proteins, which are capable of being transported across the blood-brain barrier (BBB) and comprise an alpha-L-iduronidase (IDUA) enzyme-Fc fusion polypeptide. Certain embodiments also provide methods of using such proteins to treat MPS I.

Abstract: The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform tor increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.

Abstract: Provided herein are conjugates comprising proteins that bind to a transferrin receptor and oligonucleotides that are capable of modulating the expression of a target gene or sequence, as well as methods of use thereof.

Abstract: Certain embodiments provide a fusion protein comprising an iduronate 2-sulfatase (IDS) amino acid sequence, an IDS variant amino acid sequence, or a catalytically active fragment thereof; and an anti-transferrin receptor (TfR) antibody as described herein, as well as methods of use thereof.

Abstract: Provided herein are proteins, which are capable of being transported across the blood-brain barrier (BBB) and comprise sulfoglucosamine sulfohydrolase (SGSH) enzyme-Fc fusion polypeptides. Certain embodiments also provide methods of using such proteins to treat Sanfilippo syndrome A.

Abstract: Provided herein are proteins, which are capable of being transported across the blood-brain barrier (BBB) and comprise sulfoglucosamine sulfohydrolase (SGSH) enzyme-Fc fusion polypeptides. Certain embodiments also provide methods of using such proteins to treat Sanfilippo syndrome A.

Abstract: Provided herein are fusion proteins that comprise an enzyme replacement therapy enzyme and an Fc region, as well as methods of using such proteins to treat a lysosomal storage disorder. Methods for transporting agents across the blood-brain barrier are also provided herein.

Abstract: The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform tor increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.

Abstract: The invention is directed to novel sPD-1 variant-Fc fusion proteins.

Abstract: Provided herein are compositions and methods for alleviating cancer or infection in a subject by administering a therapeutically effective amount of a pharmaceutical composition comprising an isolated PD-1 variant polypeptide. The PD-1 variant polypeptide can inhibit the activity of PD-1 by, for example, competitive or non-competitive inhibition of the interaction between wild-type PD-1 and one or more of its ligands, PD-L1 and PD-L2.

Abstract: The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform tor increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.

Abstract: The invention is directed to novel sPD-1 variant—Fc fusion proteins.

Abstract: Provided herein are compositions and methods for alleviating cancer or infection in a subject by administering a therapeutically effective amount of a pharmaceutical composition comprising an isolated PD-1 variant polypeptide. The PD-1 variant polypeptide can inhibit the activity of PD-1 by, for example, competitive or non-competitive inhibition of the interaction between wild-type PD-1 and one or more of its ligands, PD-L1 and PD-L2.

Abstract: In one aspect, antibodies that specifically bind to a human triggering receptor expressed on myeloid cells 2 (TREM2) protein are provided. In some embodiments, the antibody decreases levels of soluble TREM2 (sTREM2). In some embodiments, the antibody enhances TREM2 activity.

Abstract: In one aspect, antibodies that specifically bind to a human triggering receptor expressed on myeloid cells 2 (TREM2) protein are provided. In some embodiments, the antibody decreases levels of soluble TREM2 (sTREM2). In some embodiments, the antibody enhances TREM2 activity.

Abstract: The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform tor increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.

Abstract: The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform for increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.

Abstract: Provided herein are compositions and methods for alleviating cancer or infection in a subject by administering a therapeutically effective amount of a pharmaceutical composition comprising an isolated PD-1 variant polypeptide. The PD-1 variant polypeptide can inhibit the activity of PD-1 by, for example, competitive or non-competitive inhibition of the interaction between wild-type PD-1 and one or more of its ligands, PD-L1 and PD-L2.

Abstract: The invention is directed to novel sPD-1 variant—Fc fusion proteins.