Myeloma cells in lab, mice killed with nanoparticle-delivered RNA

System hailed as first to specifically target cancer cells in bone marrow

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Researchers at Tel Aviv University in Israel have developed a new nanoparticle system that can deliver RNA-based therapies designed to kill myeloma cells in bone marrow.

Nanoparticle-mediated delivery of an RNA therapy specifically designed to reduce levels of CKAP5 — a protein required for cancer cells to grow and multiply — was found to effectively kill myeloma cells in a lab flask and in a mouse model of the disease.

“The drug delivery system we developed is the first that specifically targets cancer cells inside the bone marrow and the first to show that silencing the [activity] of CKAP5 gene can be used to kill blood cancer cells,” Dana Tarab-Ravski, the study’s first author and a PhD student at Tel Aviv University, said in a news release.

The new technology “opens a new world for selective delivery of RNA medications and vaccines for cancer tumors and diseases originating in the bone marrow,” said Dan Peer, PhD, the study’s senior author and a professor at Tel Aviv University.

The findings were detailed in “Delivery of Therapeutic RNA to the Bone Marrow in Multiple Myeloma Using CD38-Targeted Lipid Nanoparticles,” in Advanced Science.

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RNA-based therapy as treatment for myeloma

Multiple myeloma is a rare blood cancer caused by the uncontrolled growth of plasma cells, or antibody-producing immune cells, in bone marrow.

“There are many possible treatments for this disease, but after a certain period of improvement most patients develop resistance to the therapy and the disease relapses even more aggressively,” Tarab-Ravski said. “Therefore, there is a constant need for developing new treatments for multiple myeloma.”

RNA, a molecule that’s structurally similar to DNA, is essential for most biological functions, being mainly involved in converting genetic information in DNA into proteins.

“RNA-based therapeutics are powerful and clinically approved therapeutic tools, potentially capable of inducing gene silencing, editing, or [activity] in any cell,” the researchers wrote.

The therapies can be used to promote protein production inside cells, which is the basic setup for how RNA-based COVID-19 vaccines work. Also, medications based on small interference RNA (siRNA) can suppress the production of specific proteins, such as those needed for cancer cells to grow.

“The challenge in these treatments is to reach the right cells,” said Tarab-Ravski, who noted that myeloma cells in the bone marrow are “very hard to reach.”

Researchers here created a system to deliver RNA-based therapies to myeloma cells using lipid nanoparticles — like little bubbles made of fatty molecules that can be wrapped around RNA. Lipid nanoparticles were used in RNA-based COVID-19 vaccines.

To target myeloma cells, the nanoparticles were coated with antibodies that specifically bind to CD38, a protein on the surface of these cancer cells.

As a proof-of-concept for this setup, the researchers designed the nanoparticles to carry and deliver a siRNA that would specifically suppress CKAP5’s production. The protein is found at high levels in many cancers.

The nanoparticle treatment killed roughly 90% of lab-grown human myeloma cells and 53.19% of those from people with the disease.

‘Great advantage’ of RNA-based therapy

The scientists also tested the nanoparticle system in a mouse model of multiple myeloma. In mice given a mock or inactive treatment, about 17-18% of the bone marrow was occupied by myeloma cells. But in those receiving the nanoparticle-delivered siRNA therapy, 6.99% of the bone marrow was occupied by cancer cells.

“Our study was the first to show the arrival of RNA therapy to MM [multiple myeloma] cells residing in the [bone marrow] of MM-bearing mice and achieve a robust therapeutic effect,” the researchers wrote. “Therefore, we believe our results can prove the feasibility of implementing targeted [nanoparticles] for treatment of [blood cancers].”

While the study focused on RNA-based therapy to block CKAP5, the nanoparticle system could easily be altered to target other disease-associated proteins, the researchers said.

“RNA-based therapy has a great advantage … because it can be developed very quickly,” said Tarab-Ravski, adding that “by simply changing the RNA molecule a different gene can be silenced each time, thereby tailoring the treatment to the progression of the disease and to the individual patient.”

“This therapeutic strategy opens new avenues for using RNA therapy as a novel drug class that has never been used before for treating MM and brings targeted [lipid nanoparticles] and RNA-based technologies closer to clinical application for all [blood cancers],” the scientists said.