The invention relates to a method for preparing a therapeutic
RNA platelet carrier. The method comprises at least the following steps: transducing at least one therapeutic
RNA sequence together with at least one therapeutic
RNA packaging sequence comprising an RNA
binding protein sequence to a
megakaryocyte progenitor cell and / or a hematopoietic stem and
progenitor cell expressing CD34, using
a DNA-based vehicle; the present invention relates to a therapeutic
RNA sequence and / or packaging sequence encoding at least one therapeutic RNA product in a
megakaryocyte (e.g., HSPC), an immature
megakaryocyte, and / or a megakaryocyte; activating expression of the therapeutic
RNA sequence and / or the therapeutic RNA packaging sequence; and generating platelets from a mature megakaryocyte derived from a transduced
progenitor cell of the megakaryocyte and / or a transduced hematopoietic stem and
progenitor cell (HSPC) expressing CD34 and / or a transduced immature megakaryocyte and / or a transduced megakaryocyte, wherein the expression activation step is regulated to occur during megakaryocyte maturation and / or
platelet formation wherein the generated
platelet carrier is functionally reactive to activation with a specific
agonist wherein the generated platelet carrier is activated by an
extracellular signal, and wherein the expression activation step is regulated to occur during megakaryocyte maturation and / or platelet formation. And wherein the platelet carrier produced contains the at least one therapeutic RNA product. The invention also relates to a therapeutic RNA platelet carrier engineered by the above method and its therapeutic use. In addition, the present invention relates to a pharmaceutical composition comprising an RNA platelet carrier engineered by the above method and therapeutic uses thereof.