Interfering Nanoparticles for Targeted RNA Delivery
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Solution Overview
Problem
There is a need for efficient and targeted delivery of RNAi agents in vivo and in vitro that are non-toxic, non-immunogenic, and biodegradable, with the ability to specifically target cells and tissues, as existing methods lack specificity and safety.
Innovation Solution
The use of nanotransporters, specifically interfering nanoparticles (iNOPs), which are functionalized with surface groups such as lipids, cell-type specific targeting moieties, and charge controlling molecules, to deliver RNA silencing agents, including miRNA silencing agents, to specific cells, utilizing a core structure like dendrimers or nanotubes, allowing for targeted and precise biological functions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional delivery methods are used for RNAi agents, then delivery can be achieved, but specificity and safety are insufficient
Solution Approach 1:
The delivery system is segmented into distinct functional components: a nanoparticle core (providing structural framework and surface area), surface groups (providing targeting and functional properties), and RNAi agents (providing therapeutic function). This segmentation allows each component to be optimized independently for specificity and safety.
Solution Approach 2:
The nanoparticle surface is functionalized with specific surface groups (such as cell-type specific targeting moieties, lipids, and charge controlling molecules) that provide localized functionality at the nanoparticle surface, enabling specific cell targeting and reduced off-target effects while maintaining overall system safety.
2Productivity
If RNAi agents are delivered to achieve therapeutic effect, then gene expression can be altered, but toxicity and immune response increase
Solution Approach 1:
The nanoparticle serves as an intermediary carrier that delivers RNAi agents to cells. The nanoparticle core and surface groups act as a protective interface between the therapeutic agent and the cellular environment, enabling effective gene silencing while reducing direct toxic effects and immune recognition of the agent.
Solution Approach 2:
The nanoparticle surface groups modify key parameters of the delivery system including charge, hydrophobicity, and molecular size, which alter cellular uptake mechanisms and reduce toxicity. The charge controlling molecules and lipid groups specifically adjust surface properties to enhance biocompatibility and reduce immune response.
3Productivity
If RNAi agents are delivered to achieve therapeutic effect, then gene expression can be altered, but immune response increases
Solution Approach 1:
The nanoparticle functions as a stealth intermediary that shields the RNAi agents from immune detection. The nanoparticle surface groups (particularly lipids and charge controlling molecules) create a protective barrier that reduces recognition by the immune system while still enabling effective cellular delivery and gene silencing.
4Ease of manufacture
If simple nanoparticle structures are used, then manufacturing is easier, but delivery functionality and targeting specificity are reduced
Solution Approach 1:
The nanoparticle is designed as a modular segmented structure with a core component and interchangeable surface groups. This segmentation enables standardized core synthesis followed by modular attachment of specific surface groups (lipids, targeting moieties, charge controlling molecules), maintaining ease of manufacture while enabling versatile delivery functionality through combinatorial surface group selection.
Data Source
AI summary
Provided are compositions and methods for delivery of therapeutic agents, such as chemically stabilized antisense oligonucleotides useful in RNA silencing. The compositions include interfering nanoparticles (iNOPs) associated with one or more agents. Several functional iNOP derivatives are provided which allow for targeted delivery of agents to specific cell types as well as exhibiting reduced cellular toxicity.