Lipid-Core Nanoparticle RNA Complexes for Lower Reactogenicity
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Solution Overview
Problem
Conventional nanoparticle carriers for RNA-based vaccines cause unwanted and sometimes serious side effects due to over-stimulation of the host immune system, necessitating the development of safer nanoparticle compositions that can deliver therapeutically effective amounts of RNA without systemic reactions.
Innovation Solution
The use of nanoparticles with a hydrophobic core comprising lipids in a liquid phase at 25 degrees Celsius, complexed with nucleic acids, to form nucleic acid-nanoparticle complexes, which are administered to a tissue to induce a local immune response and reduce systemic inflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional nanoparticle carriers are used for RNA delivery, then RNA delivery effectiveness is improved, but systemic immune reactions and reactogenicity worsen
Solution Approach 1:
The nanoparticle composition is designed to elicit a local immune response at the injection site while minimizing systemic effects. The formulation creates a localized inflammatory response that promotes antigen presentation and antibody production without causing widespread systemic reactogenicity, thereby achieving effective RNA delivery with reduced harmful systemic effects.
Solution Approach 2:
The patent modifies the physical and chemical parameters of the nanoparticle formulation, including lipid composition, particle size, and surface properties, to optimize the balance between RNA delivery efficiency and immune response modulation. These parameter changes enable the nanoparticles to deliver RNA effectively while controlling the magnitude and localization of the immune response.
2Productivity
If higher doses of RNA are administered, then therapeutic effectiveness is improved, but reactogenicity and safety worsen
Solution Approach 1:
The nanoparticle formulation acts as an intermediary carrier that controls the release and distribution of RNA in the body. It facilitates safe delivery of higher RNA doses by modulating the immune response, allowing therapeutic effectiveness to be achieved without proportionally increasing reactogenicity through controlled local inflammation and antigen presentation.
3Productivity
If nanoparticle composition is optimized for RNA delivery, then delivery efficiency is improved, but manufacturing complexity worsens
Solution Approach 1:
The patent employs composite nanoparticle formulations combining specific lipid components, nucleic acids, and adjuvants to achieve optimized RNA delivery. This composite approach enhances delivery efficiency through synergistic effects while maintaining manufacturing feasibility by using established techniques for assembling multi-component nanoparticle systems.
Data Source
AI summary
The disclosure provides compositions, methods of treatment, and methods of making and using compositions to deliver a nucleic acid to a subject that, optionally, have reduced reactogenicity and promotes a local innate immune response in the subject while promoting an adaptive immune response. Compositions described herein include nanoparticles, optionally including an inorganic particle, capable of admixing with nucleic acids encoding proteins, antibodies, or immunomodulators. Methods of using the compositions as a therapeutic vaccine for the treatment of an infection or cancer are also provided.