Newly developed technology makes it possible to use platelets as a transport vehicle for the storage and targeted delivery of therapeutic proteins.
Platelets circulate in the blood and contain storage particles (granules) in which numerous bioactive substances are present. These substances are released after activation. Alpha granules, which are the most common type of platelet granule, have therapeutic potential due to their specific properties as a transport vehicle. Alpha granules store more than 300 different proteins, including immune system messenger substances. The use of platelets for the administration of medicinal products has already been investigated in various applications, such as therapies to treat tumours or cardiovascular diseases or for gene therapy in cases of haemophilia. Lentiviral vectors are usually used for the permanent transfer of therapeutic genes to somatic cells. Lentiviral vectors are virus-derived gene delivery vectors that cannot reproduce. The therapeutic genes contain the blueprint for a therapeutic protein that is formed by the cells after gene transfer.
A Paul-Ehrlich-Institut research group investigated the use of platelets as a transport vehicle for therapeutic proteins and their targeted release. The group worked under the direction of Professor Ute Modlich and in cooperation with the Hannover Medical School under the direction of Professor Thomas Moritz. The research team suggested that it would be possible to achieve the targeted loading of the alpha granules by attaching suitable sorting signals to the transmitted therapeutic gene products.
Using two complex molecular biological strategies, the research team developed lentiviral vectors that possess the genetic information for transgenic proteins with such sorting signals. As predicted, therapeutic proteins were successfully stored in human and mouse alpha granules in platelet precursor cells in vitro and in mouse alpha granules in platelets in vivo. An important cytokine, the interferon alpha (IFNα), could thus be successfully stored in vivo in mouse platelets as a potentially antiviral cytokine and released by platelet activation to ward off viruses.
The newly developed vectors open up a number of new applications for cell therapy by making platelets usable as carriers for therapeutic proteins.
Prof Dr Dr Ute Modlich (Deputy Head of the Animal Facilities Unit and Head of the Gene Modification in Stem Cells Subunit)
Woods VMA, Latorre-Rey LJ, Schenk F, Rommel MGE, Moritz T, Modlich U (2022): Targeting transgenic proteins to alpha granules for platelet-directed gene therapy.
Mol Ther Nucleic Acids 27: 774-786.