Fusosome compositions and uses thereof
AssigneeFlagship Pioneering Innovations V, Inc.
InventorsGeoffrey A. von Maltzahn, Jacob Rosenblum Rubens, John Miles Milwid, Michael Travis Mee, Neal Francis Gordon, Jagesh Vijaykumar Shah
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Abstract
The present disclosure provides, at least in part, methods and compositions for in vivo fusosome delivery. In some embodiments, the fusosome comprises a combination of elements that promote specificity for target cells, e.g., one or more of a fusogen, a positive target cell-specific regulatory element, and a non-target cell-specific regulatory element. In some embodiments, the fusosome comprises one or more modifications that decrease an immune response against the fusosome.
Claims31
A fusosome comprising:
- a) a lipid bilayer comprising a paramyxovirus fusogen, wherein the paramyxovirus fusogen comprises a targeting moiety that binds a cell surface marker on a liver cell for re-targeted delivery to the liver cell;
- and
- b) a nucleic acid that comprises:
- (i) a payload gene encoding an exogenous agent;
- and
- (ii) a positive liver cell-specific regulatory element operatively linked to the payload gene, wherein the positive liver cell-specific regulatory element increases expression of the payload gene in a liver cell relative to an otherwise similar fusosome lacking the positive liver cell-specific regulatory element;
- and
- (iii) a non-target cell-specific regulatory element (NTCSRE) operatively linked to the payload gene, wherein the NTCSRE decreases expression of the payload gene in a non-liver cell relative to an otherwise similar fusosome lacking the NTCSRE, wherein the NTCSRE comprises a non-liver cell specific miRNA recognition sequence.
Dependencies are inferred from the claim text.