METHOD FOR PRODUCING MANIPULATED BLOOD PLATES

Abstract

Methods for the production of genetically modified platelets, wherein the method includes at least the following steps: - Transduction of a therapeutic sequence into megakaryocyte precursors, CD34-expressing hematopoietic stem and progenitor cells, immature megakaryocytes or megakaryocytes, using a DNA-based vector, wherein the therapeutic sequence encodes at least one therapeutic product, - Generating platelets from mature megakaryocytes derived from transduced megakaryocyte precursors or from transduced CD34-expressing hematopoietic stem and precursor cells or from transduced immature megakaryocytes or from transduced megakaryocytes, wherein the platelets contain at least one therapeutic product.

Claims

[1] A process for producing genetically modified platelets, the process comprising at least the following steps: - Transduction of a therapeutic sequence into precursors of megakaryocytes, CD34-expressing hematopoietic stem and progenitor cells, immature megakaryocytes or megakaryocytes, using a DNA-based vector, wherein the therapeutic sequence encodes at least one therapeutic product, - generating platelets from mature megakaryocytes derived from the transduced megakaryocyte precursors or from the transduced CD34-expressing hematopoietic stem and progenitor cells or from the transduced immature megakaryocytes or from the transduced megakaryocytes, wherein the platelets contain the at least one therapeutic product. [2] Method according to claim 1, characterized bythat the therapeutic sequence encodes at least one mRNA, siRNA, shRNA or miRNA. [3] Method according to claim 1 or claim 2, characterized by that the therapeutic sequence is present as a single or in tandem for multiplexing. [4] Method according to claim 2 or claim 3, characterized by that the therapeutic product is a miRNA or siRNA against podoplanin (PDPN). [5] Method according to one of claims 1 to 4, characterized by that the DNA-based vector further comprises at least one coding sequence for a receptor protein, e.g. a cell- or tissue- or organ-specific receptor protein, wherein the platelets express the receptor protein. [6] Method according to claim 5, characterized by that the receptor protein is an unmodified receptor, a receptor protein complex, a chimeric receptor protein, or a chimeric receptor protein containing a gain-of-function mutation. [7] Method according to claim 5 or claim 6, characterized by that the coding sequence for the receptor protein has an mRNA. [8] Method according to one of claims 1 to 7, characterized by that the platelets are produced for therapeutic use. [9] Use of a pharmaceutical preparation comprising genetically modified platelets expressing at least one therapeutic sequence and / or at least one coding sequence for a receptor protein in a method for treating a disease. [10] Use of a pharmaceutical preparation comprising genetically modified platelets expressing at least one therapeutic sequence and / or at least one coding sequence for a receptor protein in a method for treating cancer, acute inflammation, chronic inflammation, bleeding, coagulation and / or liver disease. [11] Use of genetically modified platelets expressing at least one therapeutic sequence and / or at least one coding sequence for a receptor protein in a method for treating a disease. [12] Use of genetically modified platelets expressing at least one therapeutic sequence and / or at least one coding sequence for a receptor protein in a method for treating cancer, acute inflammation, chronic inflammation, bleeding, coagulation and / or liver disease. [13] Pharmaceutical preparation comprising genetically modified platelets expressing at least one therapeutic sequence and / or at least one coding sequence for a receptor protein, e.g. a cell- or tissue- or organ-specific receptor protein, for use in medicine. [14] A pharmaceutical preparation comprising genetically modified platelets expressing at least one therapeutic sequence and / or at least one coding sequence for a receptor protein for use in a method of treating cancer, acute inflammation, chronic inflammation, bleeding, coagulation and / or liver disease. [15] Genetically modified platelets expressing at least one therapeutic coding sequence and / or at least one sequence for a receptor protein for use in medicine. [16] Genetically modified platelets expressing at least one therapeutic coding sequence and / or at least one sequence for a receptor protein for use in a method of treating cancer, acute inflammation, chronic inflammation, bleeding, coagulation and / or liver disease.