Compositions and methods for microglia replacement therapy
AssigneesSavanna Biotherapeutics, Inc., The Board of Trustees of the Leland Stanford Junior University
InventorsFrederick Christian Bennett, Peter A. Thompson, Mariko L. Bennett, Andy J. Jennings
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Abstract
The present disclosure provides methods and compositions for microglia replacement therapy in a subject in need thereof. In some cases, the method involves administering myeloid cells to the central nervous system of a subject. In some cases, the myeloid cells are derived from embryonic or extraembryonic tissue. In some cases, the myeloid cells are genetically modified. The genetic modification may include a colony stimulating factor 1 receptor (CSF1R) variant that is resistant to a CSF1R inhibitor, yet retains sensitivity to its ligand (e.g., CSF1, IL34).
Claims17
A composition comprising a genetically modified human myeloid cell, wherein the genetically modified human myeloid cell comprises a nucleic acid encoding a modified human Colony-Stimulating Factor 1 Receptor (CSF1R) protein comprising an amino acid substitution selected from the group consisting of:
- (i) a glycine-to-alanine substitution at an amino acid residue corresponding to an amino acid at position 795 (G795A) of SEQ ID NO:
- 3;
- ii) an aspartate-to-alanine substitution at an amino acid residue corresponding to an amino acid at position 796 (D796A) of SEQ ID NO:
- 3;
- (iii) a threonine-to-isoleucine substitution at an amino acid residue corresponding to an amino acid at position 663 (T663I) of SEQ ID NO:
- 3;
- (iv) a methionine-to-leucine substitution at an amino acid residue corresponding to an amino acid at position 637 (M637L) of SEQ ID NO:
- 3;
- and
- (v) a glycine-to-valine substitution at an amino acid residue corresponding to an amino acid at position 669 (G669V) of SEQ ID NO:
- 3.
A modified human Colony-Stimulating Factor 1 Receptor (CSF1R) polypeptide comprising an amino acid substitution selected from the group consisting of:
- (i) a glycine-to-alanine substitution at an amino acid residue corresponding to an amino acid at position 795 of SEQ ID NO:
- 3;
- (ii) an aspartate-to-alanine substitution at an amino acid residue corresponding to an amino acid at position 796 of SEQ ID NO:
- 3;
- (iii) a threonine-to-isoleucine substitution at an amino acid residue corresponding to an amino acid at position 663 of SEQ ID NO:
- 3;
- (iv) a methionine-to-leucine substitution at an amino acid residue corresponding to an amino acid at position 637 of SEQ ID NO:
- 3;
- and
- (v) a glycine-to-valine substitution at an amino acid residue corresponding to an amino acid at position 669 of SEQ ID NO:
- 3.
Dependencies are inferred from the claim text.