Denali Therapeutics Inc.

Mihalis S Kariolis

Adam P Silverman

Xiaocheng Chen

Robert C Wells

Ankita Srivastava

Cathal S Mahon

Mark S Dennis

Ryan Jefferson Watts

Joy Yu Zuchero

Anastasia Henry

Gunasekaran Kannan

Rachel Prorok

Bettina Van Lengerich

Joshua I Park

Kathryn M Monroe

Zhenyu Gu

Julie Ullman

Tina Giese

Shrishti Tyagi

Melina Lenser

Hanh Giai Ngo

Yashas Rajendra

Tianao Yuan

Provided herein are proteins, which are capable of being transported across the blood-brain barrier (BBB) and comprise an acid alpha-glucosidase (GAA) enzyme-Fc fusion polypeptide. Certain embodiments also provide methods of using such proteins to treat Pompe disease.

Fusion proteins comprising acid alpha-glucosidase enzymes and methods thereof

Provided herein are polypeptides that bind to a transferrin receptor, methods of generating such polypeptides, and methods of using the polypeptides to target a composition to a transferrin receptor-expressing cell.

Methods of engineering transferrin receptor binding polypeptides

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.

Fusion proteins comprising sulfoglucosamine sulfohydrolase enzymes and methods thereof

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.

Fusion proteins comprising enzyme replacement therapy enzymes

Engineered transferrin receptor binding polypeptides

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.

Engineered polypeptides

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.

Anti-TREM2 antibodies and methods of use thereof

Growing community of inventors

South San Francisco, CA, United States of America

Mihalis S Kariolis