(MENAFN- PR Newswire)
Megakaryocyte-derived EVs show preferential biodistribution to bone marrow, bypassing the liver Safety and tolerability data demonstrate the potential for repeat dosing
BOSTON, Dec. 11, 2023 /PRNewswire/ -- STRM , 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,
presented the first preclinical data on their novel delivery platform that uses megakaryocyte-derived EVs to target hematopoietic stem/progenitor cells (HSPCs) in the bone marrow at the American Society of Hematology (ASH) annual meeting being held in San Diego, California, December 9 – 12, 2023.
Study results demonstrate that megakaryocyte-derived EVs preferentially target bone marrow in mice and non-human primates. The EVs selectively targeted and delivered pDNA cargo to HSPCs and, following intravenous delivery, led to reporter protein expression almost exclusively in the bone marrow. Safety and tolerability data in non-human primates demonstrated amenability of the platform to repeat dosing. Collectively, these data describe a platform that can be used to develop and deliver targeted gene therapies in vivo and that will be safe for repeat dosing.
"The data we presented at ASH describe an advanced gene therapy platform that can target bone marrow following in vivo administration in both mice and non-human primates," said Laura Goldberg, M.D., Ph.D., Vice President of R&D at STRM. "This approach offers the potential to replace current ex vivo approaches to treat rare blood disorders and provides the possibility of repeat dosing as required for successful clinical outcomes and to expand the landscape of diseases that could be treated with this approach."
Study Results Presented at ASH Annual Meeting
The poster presentation at ASH, titled "Novel Bone Marrow/HSC-Targeted, Megakaryocyte-Derived Extracellular Vesicle Delivery Modality for In Vivo Gene Therapy," described a series of preclinical studies conducted in mice and non-human primates and included the following highlights:
In mouse biodistribution studies, fluorescent-labeled MkEVs were predominantly detected in bone marrow compared to the liver and spleen, with preferential targeting of the hematopoietic stem and progenitor cells as evidenced by almost 70% of hematopoietic stem and progenitor cells and >95% of long-term hematopoietic stem cells positive for EVs. In mouse protein expression studies, a fluorescent protein encoded by pDNA was detected almost exclusively in bone marrow (p<0.0001 vs. all other tissues) following intravenous delivery of the MkEVs loaded with the pDNA. In non-human primates, MkEVs and their pDNA cargo showed preferential biodistribution to bone marrow. In non-human primates, serial delivery of MkEVs was well tolerated with no evidence of kidney, hematologic or liver damage as evidenced by normal creatinine and electrolytes, no significant changes in complete blood counts, coagulation parameters, or liver function tests. Furthermore, there was no evidence of significant cytokine release or inflammatory changes on tissue histology.
"We are leveraging our platform to develop gene therapies for rare blood diseases. Our vision is to open the door to the future of medicine for patients living with rare diseases worldwide and bring gene therapy to life," said Jonathan Thon, Ph.D., CEO and Founder of STRM. "We are extremely encouraged by our preclinical data, and we look forward to continuing development of our gene delivery platform and moving this platform into the clinic."
About Extracellular Vesicles
Extracellular vesicles (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, 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.
About STRM
Based in
Cambridge MA, STRM is a pre-clinical, VC-backed biotechnology company leveraging extracellular vesicles as a platform to develop and deliver targeted gene therapies in vivo that are safe for repeat dosing. Our vision is to open the door to the future of medicine for patients living with rare diseases worldwide and bring gene therapy to life. Please visit
strm to meet our growing team of partners and collaborators and stay up to date on our progress.
SOURCE STRM
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