Fred Hutch News Service
Matthias Stephan, MD, PhD Photo by Robert Hood,
Researchers say they have created nanoparticles loaded with messenger RNA (mRNA) that can give cells the ability to fight cancers and other diseases.
To use these freeze-dried nanocarriers, the team added water and introduced the resulting mixture to cells.
The nanocarriers were able to target T cells and hematopoietic stem cells (HSCs), delivering mRNA directly to the cells and triggering short-term gene expression.
The T cells were then able to fight leukemia and lymphoma in vitro and in vivo. And the HSCs demonstrated improvements in growth and regenerative potential.
Matthias Stephan, MD, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues described this research in Nature Communications.
“We developed a nanocarrier that binds and condenses synthetic mRNA and protects it from degradation,” Dr Stephan said.
The researchers surrounded the nanocarrier with a negatively charged envelope with a targeting ligand attached to the surface so the carrier homes and binds to a particular cell type. When this happens, the cell engulfs the carrier, which can be loaded with different types of manmade mRNA.
The researchers mixed the freeze-dried nanocarriers with water and samples of cells. Within 4 hours, cells started showing signs that editing had taken effect.
The team noted that boosters can be given if needed. And the nanocarriers are made from a dissolving biomaterial, so they are removed from the body like other cell waste.
Testing the carriers
Dr Stephan and his colleagues tested their nanocarriers in 3 ways.
First, the researchers tested nanoparticles carrying a gene-editing tool to T cells that snipped out their natural T-cell receptors and was paired with genes encoding a chimeric antigen receptor (CAR).
The resulting CAR T cells maintained their ability to proliferate and successfully eliminated leukemia cells.
Next, the researchers tested nanocarriers targeted to CAR T cells and containing foxo1 mRNA. This prompted the T cells to develop into a type of memory cell with enhanced antitumor activity.
The team found these CAR T cells induced “substantial disease regression” and prolonged survival in a mouse model of B-cell lymphoma.
Finally, the researchers tested nanocarriers targeted to HSCs. The carriers were equipped with mRNA that “induced key regulators of self-renewal,” accelerating the growth and regenerative potential of the HSCs in vitro.
Future possibilities
Dr Stephan and his colleagues noted that these nanocarriers are built on existing technology and can be used by individuals without knowledge of nanotechnology. Therefore, the team hopes the nanocarriers will be an off-the-shelf way for cell-therapy engineers to develop new approaches to treat diseases.
The researchers believe the nanocarriers could replace electroporation, a multistep cell-manufacturing technique that requires specialized equipment and clean rooms. The team noted that up to 60 times more cells survive the introduction of the nanocarriers than survive electroporation.
“You can imagine taking the nanoparticles, injecting them into a patient, and then you don’t have to culture cells at all anymore,” Dr Stephan said.
He is now looking for commercial partners to move the technology toward additional applications and into clinical trials.
