Nanoparticles Loaded with mRNA Give Disease-Fighting Properties to Cells

저자：   업로드：2017-09-01  조회수：

    After they are genetically reprogrammed, easy-going immune cells can become zealous cytoreagents, or therapeutic cell transplants. The trick, however, is that the easy-going cells may not accept reprogramming so readily. For example, they may accept genetic material delivered via viral and electroporation methods only reluctantly, after much persuasion.

    A faster and easier approach is being explored by scientists based at the Fred Hutchinson Cancer Research Center. According to these scientists, a new biomedical tool using nanoparticles that deliver transient gene changes to targeted cells could make therapies for a variety of diseases -- including cancer, diabetes and HIV -- faster and cheaper to develop, and more customizable.

    Details appeared in the journal Nature Communications, in an article entitled “Hit-and-Run Programming of Therapeutic Cytoreagents Using mRNA Nanocarriers.” The article describes the development of targeted mRNA nanocarriers that can be mixed with cells to reprogram them via transient transfection. The article goes on to describe three examples to make the case that the approach is simple and generalizable.

    “First, we demonstrate that nanocarriers delivering mRNA encoding a genome-editing agent can efficiently knock-out selected genes in anti-cancer T-cells,” the article’ authors wrote. “Second, we imprint a long-lived phenotype exhibiting improved antitumor activities into T-cells by transfecting them with mRNAs that encode a key transcription factor of memory formation. Third, we show how mRNA nanocarriers can program hematopoietic stem cells with improved self-renewal properties.”

    Essentially, nanoparticles carried a gene-editing tool to T cells of the immune system that snipped out their natural T-cell receptors, and then was paired with genes encoding a chimeric antigen receptor, or CAR, a synthetic molecule designed to attack cancer.

    Next, nanoparticles were targeted to blood stem cells and equipped with mRNA that enabled the stem cells to multiply and replace blood cancer cells with healthy cells when used in bone marrow transplants.

    Finally, nanoparticles were targeted to CAR T cells and equipped with Foxo1 mRNA, which signals the anticancer T cells to develop into a type of "memory" cell that is more aggressive and destroys tumor cells more effectively and maintains antitumor activity longer.