Targeted gene delivery to non-phagocytic mammalian cells via bacterially derived intact minicells

摘要

A method of targeting bacterially-derived, intact minicells to specific, non-phagocytic mammalian cells employs bispecific ligands to deliver nucleic acids efficiently to the mammalian cells. Bispecific ligands, comprising (i) a first arm that carries specificity for a bacterially-derived minicell surface structure and (ii) a second arm that carries specificity for a non-phagocytic mammalian cell surface receptor are useful for targeting minicells to specific, non-phagocytic mammalian cells and causing endocytosis of minicells by non-phagocytic cells.

主权项

1. A targeted gene delivery method, wherein the method comprises
(a) providing a composition comprising (i) an effective dose of purified intact, bacterially derived minicells that are approximately 400 nm in diameter, comprising a plurality of therapeutic nucleic acid sequences, each operably linked to a promoter, and (ii) a bispecific antibody having specificity for a cancer cell surface receptor and specificity for the minicells, wherein said bispecific antibody is attached to said minicells, and (b) contacting said composition with non-phagocytic cancer cells, such that (i) said bispecific antibodies cause said minicells to bind to said cancer cells, (ii) said minicells are engulfed by said cancer cells, are degraded in late endosomes, and release the therapeutic nucleic acid sequences, and (iii) the therapeutic nucleic acid sequences are transported to cellular nuclei and expressed in said cancer cells.