New Nanoparticles for Delivering Large RNA Medicines to Cells

This patent describes a specific type of modified dendrimer nanoparticle designed to efficiently deliver large RNA molecules, like replicating RNA, into cells for therapeutic, prophylactic, or diagnostic purposes, notably without using cholesterol.

What it covers

This patent describes a method for delivering various agents, such as medicines or diagnostic tools, to a subject's cells using a special particle called a modified dendrimer nanoparticle (MDNP). The MDNP is built from three main parts: specific types of dendrimers (like poly(ethylene imine) or poly(propylene imine) from claim 1), a particular amphiphilic polymer (1,2-dimystistoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] from claim 1), and one or more nucleic acids (like replicating RNA or messenger RNA from claim 11) that are encapsulated inside. A key feature is that this nanoparticle specifically does not include cholesterol (claim 1). For example, these nanoparticles can deliver replicating RNAs that express proteins in cells, potentially at different rates if multiple RNAs are used (claim 3), which could be used to trigger an immune response against cancer or infectious agents (claim 15).

What it doesn't cover

• —Does not cover nanoparticles that include cholesterol in their composition, as claim 1 explicitly states the nanoparticle 'does not include cholesterol'.
• —Does not cover delivery systems using dendrimers outside the specific types and generations listed in claim 1, such as poly(ethylene imine) dendrimers beyond seven generations.
• —Does not cover nanoparticles using amphiphilic polymers other than the specific 1,2-dimystistoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] mentioned in claim 1.
• —Does not cover methods of delivery where the nucleic acids are not encapsulated within the dendrimer nanoparticle, such as direct injection of naked RNA.

The clever bit

The clever part lies in the precise, cholesterol-free formulation of the modified dendrimer nanoparticle, which allows for efficient encapsulation and delivery of large replicating RNA molecules. This specific composition enables the nanoparticles to effectively stimulate the immune system by driving the proliferation of antigen-specific T cells and boosting antibody responses, a critical function for vaccine development.

Why it matters

This patent is significant because it addresses a major challenge in medicine: safely and effectively delivering large genetic material, like RNA, into cells. The ability to deliver replicating RNA (repRNA) is particularly important for developing advanced vaccines and gene therapies that can prompt the body to produce therapeutic proteins or antigens. The inventors include prominent figures in drug delivery like Robert S. Langer, whose work has enabled numerous biomedical innovations, highlighting the potential impact of this technology on future treatments for diseases like cancer and infections.

Real-world examples

• 1.mRNA vaccines for infectious diseases (e.g., COVID-19 vaccines)
• 2.Gene therapies for genetic disorders
• 3.Oncolytic virus therapies (using replicating RNA to target cancer cells)
• 4.Immunotherapies for cancer