SELF-REPLICATING RNA VACCINES AND METHODS OF USE

Smart overview of the Invention

The application presents self-replicating RNA (srRNA) vectors designed for use in RNA vaccines or as therapeutic agents. These vectors aim to enhance RNA production, stability, translation, and pharmacokinetics, making them suitable for inducing durable immune responses. The srRNA vectors are structured to include specific sequences and elements that improve their efficacy compared to traditional non-replicating mRNA vaccines.

Background

Messenger RNA (mRNA) vaccines have shown significant potential in treating infectious diseases and cancer. There are two main types of RNA vaccines: non-replicating mRNA and self-replicating mRNA (srRNA). srRNA vaccines, derived from alphavirus genomes, are known for inducing strong immune responses. However, they face challenges such as short-term protective immunity, which necessitates structural improvements to enhance their effectiveness.

Structural Improvements

The srRNA vectors described contain several key components arranged in a specific order: a cap structure, a 5′ untranslated region (UTR), sequences encoding non-structural genes and a gene of interest (GOI), a 3′ UTR, and a poly A tail. These components are optimized to enhance the expression and immune response of the encoded antigen. The application outlines various embodiments where these components are tailored for specific antigens and therapeutic targets.

Applications and Uses

The srRNA vectors can be used to target various antigens, such as the varicella-zoster virus (VZV) antigen, SARS-CoV receptor binding protein, or human erythropoietin. The vectors are delivered using lipid nanoparticle (LNP) formulations, which improve their stability and delivery efficiency. The compositions can be administered through various routes, including intramuscular and intravenous injections, to enhance immune responses in subjects.

Potential Benefits

These improved srRNA vectors offer the potential for more potent and durable immune responses at lower doses compared to existing mRNA vaccines. They are designed to induce antigen-specific adaptive immune responses, involving B cells, CD4+ T cells, and CD8+ T cells. The application of these vectors could significantly advance the development of vaccines and therapeutics for a range of diseases.