Researchers at Tel Aviv University (TAU) say they have developed a novel technique to deliver therapeutic proteins to specific cells. They believe their method may prove useful in treating myriad malignancies, inflammatory diseases, and rare genetic disorders.

The team’s study (“Cell specific delivery of modified mRNA expressing therapeutic proteins to leukocytes”) appears in Nature Communications.

“Therapeutic alteration of gene expression in vivo can be achieved by delivering nucleic acids (e.g., mRNA, siRNA) using nanoparticles. Recent progress in modified messenger RNA (mmRNA) synthesis facilitated the development of lipid nanoparticles (LNPs) loaded with mmRNA as a promising tool for in vivo protein expression. Although progress has been made with mmRNA-LNPs based protein expression in hepatocytes, cell specificity is still a major challenge. Moreover, selective protein expression is essential for an improved therapeutic effect, due to the heterogeneous nature of diseases,” write the investigators.

“Here, we present a precision protein expression strategy in Ly6c+inflammatory leukocytes in inflammatory bowel disease (IBD) induced mice. We demonstrate a therapeutic effect in an IBD model by targeted expression of the interleukin 10 in Ly6c+ inflammatory leukocytes. A selective mmRNA expression strategy has tremendous therapeutic potential in IBD and can ultimately become a novel therapeutic modality in many other diseases.”

Over the past few years, lipid carriers encapsulating mRNAs have been shown to be extremely useful in altering the protein expressions for a host of diseases. But directing this information to specific cells has remained a major challenge.

“In our new research, we utilized mRNA-loaded carriers—nanovehicles carrying a set of genetic instructions via a biological platform called ASSET—to target the genetic instructions of an anti-inflammatory protein in immune cells,” says Dan Peer, Ph.D., director of the Laboratory of Precision Nanomedicine at the School of Molecular Cell Biology at TAU’s Faculty of Life Sciences. “We were able to demonstrate that selective anti-inflammatory protein in the target cells resulted in reduced symptoms and disease severity in colitis.

“This research is revolutionary. It paves the way for the introduction of an mRNA that could encode any protein lacking in cells, with direct applications for genetic, inflammatory, and autoimmune diseases, not to mention cancer, in which certain genes overexpress themselves.”

ASSET (Anchored Secondary scFv Enabling Targeting) uses a biological approach to direct nanocarriers into specific cells to promote gene manipulation.

“This study opens new avenues in cell-specific delivery of mRNA molecules and ultimately might introduce the specific anti-inflammatory (interleukin 10) mRNA as a novel therapeutic modality for inflammatory bowel diseases,” adds Nuphar Veiga, a graduate student at TAU. “Targeted mRNA-based protein production has both therapeutic and research applications. “Going forward, we intend to utilize targeted mRNA delivery for the investigation of novel therapeutics treating inflammation disorders, cancer, and rare genetic diseases.”

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