Specially delivered nanoparticles can program stem cells while in the body

Intermediaries get a bad rap for adding cost and complexity to surgeries. Therefore, eliminating intermediaries reduces expenses, simplifies processes, and increases efficiency and consumer happiness.

James Dahlman and his research team have been thinking along similar lines about stem cell therapy. They develop techniques that eliminate cumbersome intermediaries and may lead to new, less invasive treatments for blood disorders and genetic disorders. Avoiding the discomfort and risks of current treatments and making life easier for patients.

“This could be an alternative to invasive hematopoietic stem cell therapy; it would just need to be administered through an IV,” said Dahlman, the McAmish Early Career Professor in the Wallace H. Coulter School of Biomedical Engineering. “This simplifies the process and reduces risk to patients, which is why this study is important.”

Dahlman and a team of researchers from Georgia Tech, Emory University, and the University of California, Davis published their approach in the journal Nature Biotechnology.

take care of parents

Hematopoietic stem cells (HSCs) are like parent cells. Found in the bone marrow, it produces all types of cells needed to maintain the blood and immune system. The versatility of HSCs makes them valuable therapeutic tools in the treatment of inherited blood disorders such as sickle cell anemia, immunodeficiency, and some cancers.

HSC treatment typically involves extracting cells from a patient’s bone marrow and remanipulating them in a laboratory. During that time, patients endure chemotherapy to prepare them to receive the modified HSCs.

“While these treatments are effective, they are costly for patients,” Dr. Dahlman says. “Patients undergo chemotherapy to wipe out their immune systems, allowing their bodies to accept the therapeutic cells without resistance. This procedure can be life-threatening. We want to change this situation. I’m thinking about it.

HSCs can also be modified directly in the body. This procedure uses lipid nanoparticles (LNPs) to transfer genetic instructions to stem cells. LNPs are attached to targeting ligands, molecules designed to find specific target cells. Designing them accurately adds more time, complexity, and cost to the process. They are another intermediary, like bone marrow extraction and chemotherapy.

The researchers wanted something simpler. They discovered it in a particular nanoparticle called LNP67.

“Unlike other nanoparticle designs, this design does not require a targeting ligand,” Dahlman said. “Its chemical simplicity makes it easy to manufacture, paving the way to eventually scaling up production like mRNA vaccines.”

overcome the liver

The key to LNP67’s success is its ability to bypass the body’s main blood filter, the liver. Foreign invaders, even beneficial invaders delivered intravenously as drugs, can be captured by a healthy liver.

“The liver absorbs almost everything,” Dahlman says. “But by reducing what we capture by even 10 percent, we can double the delivery of the nanoparticle and its payload to other tissues where it is needed.”

The researchers developed 128 unique nanoparticles and narrowed down the list to 105 LNPs without targeting ligands. These were ultimately screened and evaluated for their performance in effectively and safely transmitting genetic instructions (in the form of mRNA).

LNP67 had the best performance thanks to its stealth design. For example, the surface is designed to repel proteins and other molecules that mark LNPs for capture by the liver. This feature allowed particles to circulate more uniformly through the body and reach HSCs.

“We achieved low-dose delivery without using targeting ligands, which is impressive,” Dahlman said. “This is something we’ve been working towards for years and we’re very happy to get there.”