Penn Researcher Michael Mitchell Helps Develop Nanoparticles that Target Genes in Bone Marrow
Nature Biomedical Engineering study brings together researchers at Penn and collaborators in the United States and Germany to expand the potential of RNA-based therapies beyond the liver.
Researchers at the University of Pennsylvania, MIT, Massachusetts General Hospital, and Freiburg University Heart Center in Germany have developed specialized nanoparticles capable of delivering gene-silencing therapies directly to cells in bone marrow—a significant step toward expanding the range of tissues that can be targeted with RNA-based medicines.
Published in Nature Biomedical Engineering, the study demonstrates in mice that engineered lipid-polymer nanoparticles can accumulate in bone-marrow endothelial cells and deliver small interfering RNA (siRNA) to suppress specific genes. Most nanoparticles used for RNA delivery naturally accumulate in the liver, making it difficult to target other tissues. The new approach offers a potential strategy for overcoming that limitation.
The research was co-led by Michael J. Mitchell, PhD, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering in Penn’s School of Engineering and Applied Science, alongside Marvin Krohn-Grimberghe, MD, a cardiologist affiliated with Freiburg University Heart Center in Germany, and Maximilian J. Schloss, MD, a research fellow at Massachusetts General Hospital.
Mitchell’s research focuses on engineering nanoparticles and other drug-delivery technologies capable of overcoming biological barriers that prevent therapeutics from reaching specific cells and tissues. A member of Penn’s Abramson Cancer Center and Institute for Translational Medicine and Therapeutics, Mitchell develops polymeric and lipid-based delivery systems for applications including gene regulation, genome editing, immunotherapy, and regenerative medicine. In 2018, he received an NIH Director’s New Innovator Award to develop new approaches for delivering therapeutics to the bone-marrow microenvironment, work that helped establish the foundation for this study.
Expanding RNA Delivery Beyond the Liver
Bone marrow plays a central role in producing blood and immune cells, making it an important therapeutic target for conditions ranging from cardiovascular disease to blood cancers. Yet delivering nucleic-acid therapies directly to the bone-marrow environment has remained difficult.
The researchers engineered and screened nanoparticles with different surface properties, identifying a formulation capable of avoiding predominant accumulation in the liver and lungs and instead reaching endothelial cells within bone marrow. In the study, the nanoparticles achieved substantial reductions in the expression of targeted genes.
The team tested the approach against two genes with different potential therapeutic applications. Targeting SDF1, which helps retain hematopoietic stem cells within bone marrow, demonstrated the platform’s potential to influence stem-cell mobilization—an important process for patients undergoing stem cell transplantation.
The researchers also targeted MCP1, a molecule involved in recruiting inflammatory immune cells following a heart attack. In mice, suppressing MCP1 reduced the movement of inflammatory cells from the bone marrow to the heart and improved healing of cardiac tissue following myocardial infarction.
Together, the findings demonstrate how precisely engineered nanoparticles can extend RNA interference beyond the liver and provide a platform for controlling cellular activity within the bone-marrow environment.
Connecting Penn Research with Freiburg
The study brings together expertise in bioengineering, nanomedicine, cardiovascular biology, and translational research across institutions in the United States and Germany. Collaboration with Freiburg University Heart Center connects Penn’s strengths in nanoparticle engineering and drug delivery with cardiovascular expertise in Germany, illustrating how complementary scientific approaches can converge around complex biomedical challenges.
The research also received support from U.S. and European sources, including the National Institutes of Health and the European Union’s Horizon 2020 research and innovation program, further demonstrating the international research infrastructure supporting the work.
Through support for interdisciplinary research and international engagement, the Office of the Vice Provost for Research (OVPR) helps strengthen relationships that connect Penn investigators with complementary expertise around the world. Collaborations such as this demonstrate how research partnerships across institutions and countries can accelerate emerging technologies and create new pathways toward improving human health.
Read the study in Nature Biomedical Engineering:
https://www.nature.com/articles/s41551-020-00623-7
Read the Penn Today story:
https://penntoday.upenn.edu/news/nanoparticles-can-turn-genes-bone-marrow