Researchers have developed a nanoparticle that can program stem cells while inside the body, eliminating the need for chemotherapy and bone marrow extraction in stem cell treatments.
James Dahlman and his research team have created a technique that could lead to new, less-invasive treatments for blood disorders and genetic diseases. This method avoids the discomfort and risks associated with current treatments, simplifying the process for patients.
"This would be an alternative to invasive hematopoietic stem cell therapies -- we could just give you an IV drip," says Dahlman, a professor in the Wallace H. Coulter biomedical engineering department at Georgia Tech. "It simplifies the process and reduces the risks to patients. That's why this work is important."
Dahlman and a team from Georgia Tech, Emory University, and the University of California, Davis, published their findings in the journal Nature Biotechnology.
Hematopoietic stem cells (HSCs) are parent cells located in the bone marrow, producing all types of cells necessary for blood and immune system function. HSCs are crucial in treating genetic blood diseases, including sickle cell anemia, immune deficiencies, and certain cancers.
Traditional HSC therapies involve extracting cells from the patient's bone marrow and modifying them in a lab, while the patient undergoes chemotherapy to prepare their body for the modified HSCs.
"These therapies are effective but also hard on the patients," Dahlman explains. "Patients undergo chemotherapy to wipe out their immune systems so the body will accept the therapeutic cells without a fight. The procedure can be life-threatening. We're hoping to change that."
HSCs can also be modified directly in the body using lipid nanoparticles (LNPs) to carry genetic instructions to the stem cells. The LNPs have targeting ligands that find specific target cells, adding complexity and cost to the process.
The researchers sought a simpler solution and discovered a specific nanoparticle called LNP67. "Unlike other nanoparticle designs, this one doesn't require a targeting ligand," Dahlman states. "It's chemically simple, which means it's easier to manufacture and opens the door to scaling production, like mRNA vaccines."
The success of LNP67 lies in its ability to avoid the liver, the body's primary blood filter. "The liver absorbs almost everything," Dahlman notes. "But, by reducing what it captures by even as little as 10%, we can double delivery to other tissues where the nanoparticles and their payloads are needed."
The researchers developed 128 unique nanoparticles, narrowing the list down to 105 LNPs without targeting ligands, ultimately evaluating their performance in delivering genetic instructions effectively and safely.
LNP67 emerged as the best performer due to its stealthy design, which helps it circulate evenly in the body and reach HSCs. "We achieved low-dose delivery without a target ligand, which is exciting," Dahlman adds. "This is something we've been working toward for years, and I'm very happy we got there."
Funding for this research was provided by the National Institutes of Health and the National Science Foundation. James Dahlman, Marine Z. C. Hatit, and Huanzhen Ni have filed a provisional patent related to this research (US patent application number 63/632,354).