Delivery of RNA to Different Cell Types

Smart overview of the Invention

The patent application discusses a novel method for delivering RNA to both immune and non-immune cells to enhance immunization. This approach focuses on using lipid particles to encapsulate self-replicating RNA molecules, which are then administered to vertebrates to stimulate a robust immune response. The RNA is designed to enter different cell types at the delivery site, leading to a dual effect that enhances the overall immunogenic response.

Technical Field

The innovation lies in the non-viral delivery of RNA for immunization purposes. It addresses the longstanding challenge of effectively delivering nucleic acids, such as RNA, to elicit immune responses in animals. This approach offers an alternative to traditional viral vectors and naked vaccines, aiming to improve the efficacy and safety of nucleic acid vaccines.

Mechanism of Action

The method involves administering RNA that encodes an immunogen to a specific delivery site in the body, typically muscle tissue. The RNA enters non-immune cells, like fibroblasts, and immune cells, such as macrophages and dendritic cells, that infiltrate the site. In non-immune cells, the RNA activates RNA helicases, triggering innate immune pathways and a local adjuvant effect. In immune cells, the RNA induces the expression of type I interferons and pro-inflammatory cytokines, leading to a strong immune response.

Administration Techniques

RNA can be administered through various routes, with intramuscular injection being preferred. Other methods include intradermal, subcutaneous, and intravenous administration. The RNA can be delivered as naked RNA or, preferably, combined with a delivery system like liposomes or polymer microparticles to enhance cellular entry and immune effects. Liposomes, particularly those formed from mixtures of different lipids, are emphasized as an effective delivery vehicle.

Liposome Composition

Liposomes used in this method can be formed from amphiphilic lipids, which may be anionic, cationic, or zwitterionic. The application highlights the use of specific lipids, such as DOTAP and DSPC, and the potential for PEGylation to enhance stability and prevent non-specific adsorption. A combination of DSPC, DlinDMA, PEG-DMG, and cholesterol is used as an example of an effective liposome formulation for RNA delivery.