Delivery of rna to different cell types

Abstract

RNA encoding an immunogen is co-delivered to non-immune cells at the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g. by a single injection.

1 - 16 . (canceled) 
     
     
         17 . A method of raising an immune response in a vertebrate, comprising administration of a RNA molecule to a delivery site in a vertebrate by a liposome delivery system, wherein (i) at least half of the RNA is encapsulated within the liposomes, (ii) the RNA includes fewer than 10 different species of RNA, and (iii) a RNA species encodes an immunogen and a further RNA species is a self-replicating RNA. 
     
     
         18 . The method of  claim 17 , wherein the delivery site is skeletal muscle tissue. 
     
     
         19 . The method of  claim 18 , wherein the RNA is translated by non-immune cells. 
     
     
         20 . The method of  claim 20 , wherein the immunogen can elicit an immune response against a bacterium, a virus, a fungus, or a parasite. 
     
     
         21 . The method of  claim 19 , wherein the self-replicating RNA encodes an immunogen.