STRM.BIO, a pre-clinical, VC-backed biotechnology company that is leveraging extracellular vesicles (EVs) to deliver gene therapies and developing new therapeutics for rare blood diseases, today presented the first preclinical data on the company’s novel delivery platform for in vivo gene therapy that uses megakaryocyte-derived EVs to target bone marrow hematopoietic stem cells at the 2023 Cell & Gene Meeting on the Mesa being held in Carlsbad, California.
Mouse and non-human primate studies showed preferential targeting and selective delivery of pDNA cargo to long-term bone marrow hematopoietic stem and progenitor cells (HSPCs), and reporter gene expression in mice following intravenous injection of megakaryocyte-derived EVs. Transgene expression in mice was predominantly in the bone marrow, with almost no expression detected in the liver, and no or significantly lower expression in other tissues including spleen.
Safety and tolerability data in non-human primates demonstrated amenability of the platform to repeat dosing. Preclinical studies showed no platelet elevation, no impact on coagulation parameters, and no liver or kidney toxicity. Blood counts and cytokine expression remained normal, and there was no evidence of inflammation or perturbed hematopoiesis.
Allogeneic megakaryocyte-derived EVs are produced by the company using a scalable process starting from CD34+ hematopoietic stem cells. Additional data shared at the meeting showed that the large cargo capacity of the EVs enabled tunable loading with pDNA, mRNA, and protein which enables accommodation of a variety of disease-specific payloads.
“In vivo delivery is the limiting factor in gene delivery,” said Jonathan Thon, Ph.D., CEO of STRM.BIO. “The data we presented today reinforce the potential of megakaryocyte-derived EVs to be a transformative platform for development of highly targeted in vivo delivery of gene therapies. Moreover, use of these EVs enables the possibility of repeat dosing, greatly expanding the landscape of diseases that could be treated with this approach.”
EVs are lipid-based particles that are naturally secreted by almost all cell types and include exosomes which are small vesicles that derive from inside cells, and microvesicles, which are larger and bud from the cell surface membrane. These vesicles have an innate ability to encapsulate RNA, DNA, and proteins and may be more efficient in delivering this cargo into cells compared to lipid nanoparticles and other synthetic particles in vivo.
Microvesicles inherit the complex combination of surface proteins expressed by their parent cell; as such, microvesicles derived from different cell types have different cell tropisms, making them a highly tunable option for diverse gene therapy applications. Some microvesicles, such as megakaryocyte-derived EVs, have an innate ability to home to HSPCs in the bone marrow and other locations, offering the prospect of long-lasting in vivo treatments and even cures for inherited hematopoietic disorders. Cell tropism can be further tuned by genetically engineering the microvesicle source cells to knock out or modify undesirable cell surface proteins.
Source – PRNewswire