Nanoparticle Co-Delivery of siRNA and mRNA for Coordinated Gene Control
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Solution Overview
Problem
Efficient delivery of nucleic acids, such as siRNA and mRNA, to target tissues for simultaneous suppression and expression of target genes remains a key challenge in therapeutic and vaccine applications.
Innovation Solution
Development of nanoparticles that co-deliver inhibitory nucleic acids, like siRNA, and nucleic acids encoding proteins or peptides, using polymeric or lipid-polymer hybrid nanoparticles, which can target specific cellular processes and enhance the biological activity of both nucleic acid species when delivered together.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If separate delivery systems are used for siRNA and mRNA, then each nucleic acid can be delivered effectively, but the complexity of the delivery system increases and coordination of simultaneous suppression and expression is difficult
Solution Approach 1:
The patent combines siRNA and mRNA into a single nanoparticle delivery system, allowing both nucleic acids to be transported simultaneously to the target cell. This merging approach maintains effective delivery of each component while reducing the overall complexity compared to using separate delivery systems for each nucleic acid type.
Solution Approach 2:
The nanoparticle delivery system is designed to be universal, capable of encapsulating and delivering multiple types of nucleic acids (siRNA, mRNA, and other functional nucleic acids) through a single platform. This multi-functionality allows the system to achieve both gene suppression and expression simultaneously without requiring multiple specialized delivery vehicles.
2Adaptability or versatility
If multiple nucleic acid species are delivered simultaneously, then both gene suppression and expression can be achieved, but the challenge of efficient co-delivery and coordination increases
Solution Approach 1:
The patent merges multiple functional nucleic acid species (siRNA for suppression, mRNA for expression, and optionally other functional nucleic acids) into a single nanoparticle formulation. This combining strategy enables simultaneous delivery to achieve both gene suppression and expression functions, enhancing therapeutic versatility while managing co-delivery complexity through a unified delivery platform.
Solution Approach 2:
The nanoparticle system is designed with segmented functional zones: a core region for encapsulating hydrophobic nucleic acids like siRNA, and surface or peripheral regions for accommodating hydrophilic nucleic acids like mRNA. This segmentation allows different nucleic acid types to be packaged efficiently in their optimal environments within the same particle, facilitating coordinated delivery without excessive complexity.
3Reliability
If nanoparticles are used for co-delivery, then simultaneous suppression and expression can be achieved, but formulation and characterization complexity increases
Solution Approach 1:
The patent employs composite nanoparticle materials combining hydrophobic and hydrophilic components in a unified structure. The hydrophobic core accommodates siRNA while the hydrophilic surface or peripheral regions accommodate mRNA, creating a composite material system that enables reliable co-delivery of multiple nucleic acid types through a single formulation process.
Solution Approach 2:
The nanoparticle formulation utilizes parameter changes in particle size, surface charge, and compositional ratios to optimize the packaging and release of different nucleic acid types. By adjusting these parameters, the system achieves efficient co-delivery of siRNA and mRNA while maintaining manufacturability through controlled variation of formulation parameters rather than fundamentally complex processes.
Data Source
AI summary
Nanoparticulate pharmaceutical formulations and methods for co-delivery of two or more species of nucleic acids for simultaneous suppression and expression of target genes in a cell, are provided. The nanoparticles encapsulate two or more nucleic acid species. The first nucleic acid suppresses expression of a gene or product thereof, e.g., inhibitory nucleic acid, such as antisense, siRNA, miRNA, Dicer siRNA, piRNA, etc. The second nucleic acid increases expression of, or encodes, an endogenous or exogenous protein or polypeptide, e.g., an mRNA. The first and second nucleic acid species simultaneously target or affect the same or different cellular processes within a cell including communication, senescence, DNA repair, gene expression, metabolism, necrosis, and apoptosis.