Abstract: The technology described herein is directed to compositions comprising antibodies and antibody reagent that binds specifically to Mfsd2A and method of using such compositions, e.g., to increase blood-brain barrier permeability in therapeutic methods.

Abstract: The present disclosure provides single- or double-stranded interfering RNA molecules (e.g., siRNA) that target a SiglecS (CD33) gene. The interfering RNA molecules may contain specific patterns of nucleoside modifications and internucleoside linkage modifications, as pharmaceutical compositions including the same. The siRNA molecules may be branched siRNA molecules, such as di-branched, tri-branched, or tetra-branched siRNA molecules. The disclosed siRNA molecules may further feature a 5? phosphorus stabilizing moiety and/or a hydrophobic moiety. Additionally, the disclosure provides methods for delivering the siRNA molecule of the disclosure to the central nervous system of a subject, such as a subject identified as having a neuroinflammatory disease (e.g., Alzheimer's disease).

Abstract: Described herein are methods relating to the treatment of certain diseases with an agonist of Mfsd2A, and the treatment of certain other diseases with an inhibitor of Mfsd2A.

Abstract: Microglia are an essential part of the immune system in the central nervous system, as well as potential sources of disease. Gene silencing employs short interfering RNA (siRNA) to selectively target genes that are the source of such diseases. By employing branched siRNA, distribution of the siRNA throughout the CNS, including to the resident microglial cells, may be enhanced as compared to unbranched siRNA. Methods and compositions for the use of branched siRNA in a therapy are contained herein.

Abstract: The technology described herein is directed to compositions comprising antibodies and antibody reagent that binds specifically to Mfsd2A and method of using such compositions, e.g., to increase blood-brain barrier permeability in therapeutic methods.