Autoimmune disorders are among the most prevalent chronic diseases across the globe. Emerging treatments for autoimmune disorders focus on “adoptive cell therapies,” or those using cells from a patient’s own body to achieve immunosuppression. These therapeutic cells are recognized by the patient’s body as “self,” therefore limiting side effects, and are specifically engineered to localize the intended therapeutic effect.

In treating autoimmune diseases, current adoptive cell therapies have largely centered around the regulatory T cell (Treg). Although Tregs offer great potential, using them for therapeutic purposes remains a major challenge. In particular, current delivery methods result in inefficient engineering of T cells.

Tregs only compose approximately 5-10% of circulating peripheral blood mononuclear cells. Furthermore, Tregs lack more specific surface markers that differentiate them from other T cell populations. These hurdles make it difficult to harvest, purify, and grow Tregs to therapeutically relevant numbers.

Now, a research team led by Michael Mitchell, associate professor in Bioengineering in the School of Engineering and Applied Science, has developed a lipid nanoparticle (LNP) platform to deliver Foxp3 messenger RNA (mRNA) to T cells for applications in autoimmunity. Their findings are published in the journal Nano Letters.

“The major challenges associated with ex vivo (outside the body) cell engineering are efficiency, toxicity, and scale-up: our mRNA lipid nanoparticles (mRNA LNPs) allow us to overcome all of these issues,” says Mitchell. “Our work’s novelty comes from three major components: first, the use of mRNA, which allows for the generation of transient immunosuppressive cells; second, the use of LNPs, which allow for effective delivery of mRNA and efficient cell engineering; and last, the ex vivo engineering of primary human T cells for autoimmune diseases, offering the most direct pipeline for clinical translation of this therapy from bench to bedside.”

“To our knowledge, this is one of the first mRNA LNP platforms that has been used to engineer T cells for autoimmune therapies,” Mitchell says. “Broadly, this platform can be used to engineer adoptive cell therapies for specific autoimmune diseases and can potentially be used to create therapeutic avenues for allergies, organ transplantation and beyond.”