Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.

Synthetic alphavirus-derived replicon expression systems comprising nucleic acid sequences encoding at least one modified nonstructural protein, and synthetic nucleic acid sequences encoding at least one heterologous protein are described. Methods of producing at least one heterologous protein in a cell, or of inducing an immune response in a subject by administering and/or expressing the synthetic alphavirus-derived replicon expression systems are provided.

Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic coronavirus proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.

Described herein are compositions for delivering a therapeutic or vaccine. Also described herein are methods for using the compositions described herein for delivering a therapeutic or a vaccine.

The invention relates to RNA constructs, and particularly, although not exclusively, to mRNA constructs and saRNA replicons and to nucleic acids and expression vectors encoding such RNA constructs. The invention extends to the use of such RNA constructs in therapy, for example in treating diseases and/or in vaccine delivery. The invention extends to pharmaceutical compositions comprising such RNA constructs, and methods and uses thereof.

The present invention includes nucleic acids, proteins, Chikungunya virus (CHIKV) Virus Like Particles (VLP), and methods of making a Chikungunya virus (CHIKV) Virus Like Particles (VLP) comprising: inserting one or more nucleic acids into a lentiviral backbone, wherein the nucleic acid encodes one or more Chikungunya virus (CHIKV) proteins; transfecting the one or more nucleic acids into the lentiviral backbone into a cell line; culturing the transfected cell line under conditions in which the Chikungunya virus (CHIKV) Virus Like Particles (VLP) are released from the cell line; and isolating the Chikungunya virus (CHIKV) Virus Like Particles (VLP) from a culture supernatant.

Immunomodulatory compositions that include at least one alphavirus capsid protein and methods of using such immunomodulatory compositions. In one aspect, methods of immunomodulating IL-1/TLR signaling in a cell are provided. Such methods typically include contacting the cell with an alphavirus capsid protein or a portion thereof, thereby immunomodulating IL-1/TLR signaling in the cell.

The present invention provides modified alphaviruses and compositions, methods, and kits for preparing and using them to elicit an immune response to an alphavirus in a subject.

Synthetic alphavirus-derived replicon expression systems comprising nucleic acid sequences encoding at least one modified nonstructural protein, and synthetic nucleic acid sequences encoding at least one heterologous protein are described. Methods of producing at least one heterologous protein in a cell, or of inducing an immune response in a subject by administering and/or expressing the synthetic alphavirus-derived replicon expression systems are provided.

The present disclosure relates to methods for transiently activating temperature-sensitive agents in one or more cells, for example by contacting one or more cells with a temperature-sensitive agent and transiently incubating the cells at a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. Additionally, the present disclosure relates to methods of contacting one or more cells in a subject with a temperature-sensitive agent and then lowering the subject's core body temperature to a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. The disclosure also relates to methods of contacting one or more cells in a subject with a temperature-sensitive agent, maintaining the subject's surface body temperature at a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. Further disclosed are methods of treating a subject with a temperature-sensitive therapeutic agent.